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Goyal S, Tibrewal S, Ratna R, Vanita V. Genetic and environmental factors contributing to anophthalmia and microphthalmia: Current understanding and future directions. World J Clin Pediatr 2025; 14:101982. [DOI: 10.5409/wjcp.v14.i2.101982] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2024] [Revised: 02/19/2025] [Accepted: 02/25/2025] [Indexed: 03/18/2025] Open
Abstract
Anophthalmia is defined as a complete absence of one eye or both the eyes, while microphthalmia represents the presence of a small eye within the orbit. The estimated birth prevalence for anophthalmia is approximately 3 per 100000 live births, and for microphthalmia, it is around 14 per 100000 live births. However, combined evidence suggests that the prevalence of these malformations could be as high as 30 per 100000 individuals. Microphthalmia is reported to occur in 3.2% to 11.2% of blind children. Anophthalmia and microphthalmia (A/M) are part of a phenotypic spectrum alongside ocular coloboma, hypothesized to share a common genetic basis. Both A/M can occur in isolation or as part of a syndrome. Their complex etiology involves chromosomal aberrations, monogenic inheritance pattern, and the contribution of environmental factors such as gestational-acquired infections, maternal vitamin A deficiency (VAD), exposure to X-rays, solvent misuse, and thalidomide exposure. A/M exhibit significant clinical and genetic heterogeneity with over 90 genes identified so far. Familial cases of A/M have a complex genetic basis, including all Mendelian modes of inheritance, i.e., autosomal dominant, recessive, and X-linked. Most cases arise sporadically due to de novo mutations. Examining gene expression during eye development and the effects of various environmental variables will help us better understand the phenotypic heterogeneity found in A/M, leading to more effective diagnosis and management strategies. The present review focuses on key genetic factors, developmental abnormalities, and environmental modifiers linked with A/M. It also emphasizes at potential research areas including multiomic methods and disease modeling with induced pluripotent stem cell technologies, which aim to create innovative treatment options.
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Affiliation(s)
- Shiwali Goyal
- Department of Ophthalmic Genetics and Visual Function Branch, National Eye Institute, Rockville, MD 20852, United States
| | - Shailja Tibrewal
- Department of Pediatric Ophthalmology, Dr. Shroff’s Charity Eye Hospital, New Delhi 110002, Delhi, India
- Department of Ocular Genetics (Center for Unknown and Rare Eye Diseases), Dr. Shroff’s Charity Eye Hospital, New Delhi 110002, Delhi, India
| | - Ria Ratna
- Department of Ocular Genetics (Center for Unknown and Rare Eye Diseases), Dr. Shroff’s Charity Eye Hospital, New Delhi 110002, Delhi, India
| | - Vanita Vanita
- Department of Human Genetics, Guru Nanak Dev University, Amritsar 143005, Punjab, India
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Bonell A, G. Ioannou L, Sesay A, A. Murray K, Bah B, Jeffries D, E. Moore S, Vicero-Cabrera A, S Maxwell N, E Hirst J, Tan C, Saucy A, Watters D, Sonko B, Okoh E, Idris Y, Oluwatosin Adefila W, Manneh J, Leigh-Nabou M, Bojang S, Flouris A, Haines A, Prentice A, N Sferruzzi-Perri A. Study protocol for an observational cohort study of heat stress impacts in pregnancy in The Gambia, West Africa. Wellcome Open Res 2025; 9:624. [PMID: 39925648 PMCID: PMC11803196 DOI: 10.12688/wellcomeopenres.23172.2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/06/2025] [Indexed: 02/11/2025] Open
Abstract
Climate change has resulted in an increase in heat exposure globally. There is strong evidence that this increased heat stress is associated with poor maternal and fetal outcomes, especially in vulnerable populations. However, there remains poor understanding of the biological pathways and mechanisms involved in the impact of heat in pregnancy. This observational cohort study of 764 pregnant participants based in sub-Saharan Africa, a geographical region at risk of extreme heat events, aims to evaluate the physiological and biochemical changes that occur in pregnancy due to heat stress. The key objectives of the study are to 1) map exposure to heat stress in the cohort and understand what environmental, social and community factors increase the risk of extreme heat exposure; 2) assess the impact of heat stress on maternal health, e.g. heat strain, subjective psychological well-being, sleep and activity level; 3) evaluate how heat stress impacts placenta structure and function; 4) determine how chronic heat exposure impacts birth outcomes; and 5) explore the epigenetic changes in the placenta and infant by heat stress exposure per trimester. Pregnant women will be recruited from two distinct regions in The Gambia to exploit the naturally occurring heat gradient across the country. Microclimate mapping of the area of recruitment will give detailed exposure measurements. Participants will be asked to wear a watch-style device at 28- and 35-weeks gestational age to evaluate maternal heart rate, activity and sleep. At the end of the week, an ultrasound scan will be performed to evaluate fetal size and placental blood flow. At delivery, birth outcomes will be recorded and maternal, placental and cord samples taken for epigenetic, biochemical and histological evaluation. Evaluation of neuro-behaviour and final infant samples will be taken at 1 month following birth.
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Affiliation(s)
- Ana Bonell
- Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Banjul, Banjul, The Gambia
- Centre on Climate Change and Planetary Health, London School of Hygiene and Tropical Medicine Faculty of Epidemiology and Population Health, London, England, UK
| | - Leonidas G. Ioannou
- Department of Physical Education and Sport Science, FAME laboratory, Thessaly, Greece
| | - Abdul Sesay
- Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Banjul, Banjul, The Gambia
| | - Kris A. Murray
- Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Banjul, Banjul, The Gambia
- Centre on Climate Change and Planetary Health, London School of Hygiene and Tropical Medicine Faculty of Epidemiology and Population Health, London, England, UK
| | - Bubacarr Bah
- Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Banjul, Banjul, The Gambia
| | - David Jeffries
- Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Banjul, Banjul, The Gambia
| | - Sophie E. Moore
- Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Banjul, Banjul, The Gambia
- King's College London Department of Women & Children's Health, London, England, UK
| | - Ana Vicero-Cabrera
- Institute of Social and Preventative Medicine, University of Bern, Bern, Switzerland
- University of Bern Oeschger Centre for Climate Change Research, Bern, Canton of Bern, Switzerland
| | - Neil S Maxwell
- Environmental Extremes Laboratory, University of Brighton, Brighton, England, UK
| | - Jane E Hirst
- The George Institute for Global Health UK, Imperial College London, London, UK, Oxford, England, UK
| | - Cally Tan
- Centre on Climate Change and Planetary Health, London School of Hygiene and Tropical Medicine Faculty of Epidemiology and Population Health, London, England, UK
| | - Apolline Saucy
- University of Bern Oeschger Centre for Climate Change Research, Bern, Canton of Bern, Switzerland
| | - Dorothy Watters
- Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Banjul, Banjul, The Gambia
| | - Bakary Sonko
- Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Banjul, Banjul, The Gambia
| | - Emmanuel Okoh
- Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Banjul, Banjul, The Gambia
| | - Yahaya Idris
- Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Banjul, Banjul, The Gambia
| | - Williams Oluwatosin Adefila
- Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Banjul, Banjul, The Gambia
| | - Jarra Manneh
- Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Banjul, Banjul, The Gambia
| | - Mam Leigh-Nabou
- Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Banjul, Banjul, The Gambia
| | - Sainabou Bojang
- Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Banjul, Banjul, The Gambia
| | - Andreas Flouris
- Department of Physical Education and Sport Science, FAME laboratory, Thessaly, Greece
| | - Andy Haines
- Centre on Climate Change and Planetary Health, London School of Hygiene and Tropical Medicine Faculty of Epidemiology and Population Health, London, England, UK
| | - Andrew Prentice
- Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Banjul, Banjul, The Gambia
| | - Amanda N Sferruzzi-Perri
- Centre for Trophoblast Research, University of Cambridge Department of Physiology Development and Neuroscience, Cambridge, England, UK
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LaPointe S, Beagle LE, Zheng X, Kancherla V, Mutic A, Chang HH, Gaskins AJ. Associations between exposure to extreme ambient heat and neural tube defects in Georgia, USA: A population-based case-control study. ENVIRONMENTAL RESEARCH 2024; 261:119756. [PMID: 39117054 PMCID: PMC11390300 DOI: 10.1016/j.envres.2024.119756] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Revised: 07/18/2024] [Accepted: 08/06/2024] [Indexed: 08/10/2024]
Abstract
INTRODUCTION The association between extreme ambient heat exposures during pregnancy and neural tube defects (NTDs) in offspring remains unclear. This study sought to estimate the association between exposure to extreme ambient heat during periconception and NTDs. METHODS This population-based case-control study in Georgia, USA (1994-2017) included 825 isolated NTD cases (473 anencephaly, 352 spina bifida) and 3,300 controls matched 1:4 on county of residence and time period of delivery. Daily ambient temperature data were linked to fetal death and birth records by county of residence. Extreme ambient heat exposure was defined as the number of consecutive days the daily apparent temperature exceeded the county-specific 95th percentile (derived over 1980-2010) during an eight-week periconception period. We calculated adjusted odds ratios (aORs) and 95% confidence intervals (CI) using conditional logistic regression models adjusted for maternal age, education, and ethnicity and month and year of last menstrual period. RESULTS The aORs for NTDs were 1.09 (95% CI 1.01, 1.17), 1.18 (95% CI 1.03, 1.36), and 1.29 (95% CI 1.04, 1.58) for exposure to 1-2, 3-5, and 6 or more consecutive days with apparent ambient temperatures exceeding the county-specific 95th percentile during periconception, respectively, compared to no days of extreme ambient heat exposure. Weekly analysis of extreme heat exposure indicated consistently elevated odds of offspring NTDs during periconception. These results were largely driven by spina bifida cases. CONCLUSIONS Our results highlight potential health threats posed by increasing global average temperatures for pregnant people with implications for increased risk of neural tube defects in their offspring.
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Affiliation(s)
- Sarah LaPointe
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA
| | - Lauren E Beagle
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA
| | - Xiaping Zheng
- Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, USA
| | - Vijaya Kancherla
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA
| | - Abby Mutic
- Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, GA, USA
| | - Howard H Chang
- Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, USA
| | - Audrey J Gaskins
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
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Pavlikova Z, Zahradnicek O, Jelinek Michaelidesova A, Sramek J, Davidkova M, Hovorakova M. Effect of elevated temperature and hydrocortisone addition on the proliferation of fibroblasts. Histochem Cell Biol 2024; 162:231-244. [PMID: 38801536 PMCID: PMC11322275 DOI: 10.1007/s00418-024-02295-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/25/2024] [Indexed: 05/29/2024]
Abstract
Hyperthermia along with hydrocortisone (HC) are proven teratogens that can negatively influence embryo development during early pregnancy. Proliferation of cells is one of the main developmental processes during the early embryogenesis. This study was focused on testing the effect of elevated temperature and HC addition on proliferation of cells in in vitro cultures. The V79-4 cell line was treated with HC and cultured in vitro at 37 °C or 39 °C, respectively. To reveal the effect of both factors, the proliferation of cells cultured under different conditions was evaluated using various approaches (colony formation assay, generation of growth curves, computation of doubling times, and mitotic index estimation). Our results indicate that a short-term exposure to elevated temperature slightly stimulates and a long-term exposure suppresses cell proliferation. However, HC (0.1 mg/ml) acts as a stimulator of cell proliferation. Interestingly, the interaction of HC and long-term elevated temperature (39 °C) exposure results in at least partial compensation of the negative impact of elevated temperature by HC addition and in higher proliferation if compared with cells cultured at 39 °C without addition of HC.
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Affiliation(s)
- Zuzana Pavlikova
- Institute of Histology and Embryology, First Faculty of Medicine, Charles University, Prague, Czech Republic
- Department of Anthropology and Human Genetics, Faculty of Science, Charles University, Prague, Czech Republic
| | - Oldrich Zahradnicek
- Department of Radiation Dosimetry, Nuclear Physics Institute, Czech Academy of Sciences, Prague, Czech Republic
| | - Anna Jelinek Michaelidesova
- Department of Radiation Dosimetry, Nuclear Physics Institute, Czech Academy of Sciences, Prague, Czech Republic
| | - Jaromir Sramek
- Institute of Histology and Embryology, First Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Marie Davidkova
- Department of Radiation Dosimetry, Nuclear Physics Institute, Czech Academy of Sciences, Prague, Czech Republic
| | - Maria Hovorakova
- Institute of Histology and Embryology, First Faculty of Medicine, Charles University, Prague, Czech Republic.
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Lang LI, Wang ZZ, Liu B, Chang-Qing SHEN, Jing-Yi TU, Shi-Cheng WANG, Rui-Ling LEI, Si-Qi PENG, Xiong XIAO, Yong-Ju ZHAO, Qiu XY. The effects and mechanisms of heat stress on mammalian oocyte and embryo development. J Therm Biol 2024; 124:103927. [PMID: 39153259 DOI: 10.1016/j.jtherbio.2024.103927] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Revised: 07/15/2024] [Accepted: 07/20/2024] [Indexed: 08/19/2024]
Abstract
The sum of nonspecific physiological responses exhibited by mammals in response to the disruption of thermal balance caused by high-temperature environments is referred to as heat stress (HS). HS affects the normal development of mammalian oocyte and embryos and leads to significant economic losses. Therefore, it is of great importance to gain a deep understanding of the mechanisms underlying the effects of HS on oocyte and embryonic development and to explore strategies for mitigating or preventing its detrimental impacts in the livestock industry. This article provides an overview of the negative effects of HS on mammalian oocyte growth, granulosa cell maturation and function, and embryonic development. It summarizes the mechanisms by which HS affects embryonic development, including generation of reactive oxygen species (ROS), endocrine disruption, the heat shock system, mitochondrial autophagy, and molecular-level alterations. Furthermore, it discusses various measures to ameliorate the effects of HS, such as antioxidant use, enhancement of mitochondrial function, gene editing, cultivating varieties possessing heat-resistant genes, and optimizing the animals'rearing environment. This article serves as a valuable reference for better understanding the relationship between HS and mammalian embryonic development as well as for improving the development of mammalian embryos and economic benefits under HS conditions in livestock production.
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Affiliation(s)
- L I Lang
- College of Animal Science and Technology, Southwest University, Chongqing Key Laboratory of Herbivore Science, Chongqing, 400715, China
| | - Zhen-Zhen Wang
- College of Animal Science and Technology, Southwest University, Chongqing Key Laboratory of Herbivore Science, Chongqing, 400715, China
| | - Bin Liu
- College of Animal Science and Technology, Southwest University, Chongqing Key Laboratory of Herbivore Science, Chongqing, 400715, China
| | - S H E N Chang-Qing
- College of Animal Science and Technology, Southwest University, Chongqing Key Laboratory of Herbivore Science, Chongqing, 400715, China
| | - T U Jing-Yi
- College of Animal Science and Technology, Southwest University, Chongqing Key Laboratory of Herbivore Science, Chongqing, 400715, China
| | - W A N G Shi-Cheng
- College of Animal Science and Technology, Southwest University, Chongqing Key Laboratory of Herbivore Science, Chongqing, 400715, China
| | - L E I Rui-Ling
- College of Animal Science and Technology, Southwest University, Chongqing Key Laboratory of Herbivore Science, Chongqing, 400715, China
| | - P E N G Si-Qi
- College of Animal Science and Technology, Southwest University, Chongqing Key Laboratory of Herbivore Science, Chongqing, 400715, China
| | - X I A O Xiong
- College of Veterinary Medicine, Southwest University, Chongqing, 400715, China
| | - Z H A O Yong-Ju
- College of Animal Science and Technology, Southwest University, Chongqing Key Laboratory of Herbivore Science, Chongqing, 400715, China
| | - Xiao-Yan Qiu
- College of Animal Science and Technology, Southwest University, Chongqing Key Laboratory of Herbivore Science, Chongqing, 400715, China.
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Brink N, Lakhoo DP, Solarin I, Maimela G, von Dadelszen P, Norris S, Chersich MF. Impacts of heat exposure in utero on long-term health and social outcomes: a systematic review. BMC Pregnancy Childbirth 2024; 24:344. [PMID: 38704541 PMCID: PMC11069224 DOI: 10.1186/s12884-024-06512-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Accepted: 04/11/2024] [Indexed: 05/06/2024] Open
Abstract
BACKGROUND Climate change, particularly global warming, is amongst the greatest threats to human health. While short-term effects of heat exposure in pregnancy, such as preterm birth, are well documented, long-term effects have received less attention. This review aims to systematically assess evidence on the long-term impacts on the foetus of heat exposure in utero. METHODS A search was conducted in August 2019 and updated in April 2023 in MEDLINE(PubMed). We included studies on the relationship of environmental heat exposure during pregnancy and any long-term outcomes. Risk of bias was assessed using tools developed by the Joanna-Briggs Institute, and the evidence was appraised using the GRADE approach. Synthesis without Meta-Analysis (SWiM) guidelines were used. RESULTS Eighteen thousand six hundred twenty one records were screened, with 29 studies included across six outcome groups. Studies were mostly conducted in high-income countries (n = 16/25), in cooler climates. All studies were observational, with 17 cohort, 5 case-control and 8 cross-sectional studies. The timeline of the data is from 1913 to 2019, and individuals ranged in age from neonates to adults, and the elderly. Increasing heat exposure during pregnancy was associated with decreased earnings and lower educational attainment (n = 4/6), as well as worsened cardiovascular (n = 3/6), respiratory (n = 3/3), psychiatric (n = 7/12) and anthropometric (n = 2/2) outcomes, possibly culminating in increased overall mortality (n = 2/3). The effect on female infants was greater than on males in 8 of 9 studies differentiating by sex. The quality of evidence was low in respiratory and longevity outcome groups to very low in all others. CONCLUSIONS Increasing heat exposure was associated with a multitude of detrimental outcomes across diverse body systems. The biological pathways involved are yet to be elucidated, but could include epigenetic and developmental perturbations, through interactions with the placenta and inflammation. This highlights the need for further research into the long-term effects of heat exposure, biological pathways, and possible adaptation strategies in studies, particularly in neglected regions. Heat exposure in-utero has the potential to compound existing health and social inequalities. Poor study design of the included studies constrains the conclusions of this review, with heterogenous exposure measures and outcomes rendering comparisons across contexts/studies difficult. TRIAL REGISTRATION PROSPERO CRD 42019140136.
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Affiliation(s)
- Nicholas Brink
- Climate and Health Directorate, Wits RHI, University of the Witwatersrand, Johannesburg, South Africa.
| | - Darshnika P Lakhoo
- Climate and Health Directorate, Wits RHI, University of the Witwatersrand, Johannesburg, South Africa
| | - Ijeoma Solarin
- Climate and Health Directorate, Wits RHI, University of the Witwatersrand, Johannesburg, South Africa
| | - Gloria Maimela
- Climate and Health Directorate, Wits RHI, University of the Witwatersrand, Johannesburg, South Africa
| | | | - Shane Norris
- MRC Developmental Pathways for Health Research Unit, University of the Witwatersrand, Johannesburg, South Africa
| | - Matthew F Chersich
- Climate and Health Directorate, Wits RHI, University of the Witwatersrand, Johannesburg, South Africa
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Bonell A, Part C, Okomo U, Cole R, Hajat S, Kovats S, Sferruzzi-Perri AN, Hirst JE. An expert review of environmental heat exposure and stillbirth in the face of climate change: Clinical implications and priority issues. BJOG 2024; 131:623-631. [PMID: 37501633 DOI: 10.1111/1471-0528.17622] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Accepted: 07/11/2023] [Indexed: 07/29/2023]
Abstract
Exposure to extreme heat in pregnancy increases the risk of stillbirth. Progress in reducing stillbirth rates has stalled, and populations are increasingly exposed to high temperatures and climate events that may further undermine health strategies. This narrative review summarises the current clinical and epidemiological evidence of the impact of maternal heat exposure on stillbirth risk. Out of 20 studies, 19 found an association between heat and stillbirth risk. Recent studies based in low- to middle-income countries and tropical settings add to the existing literature to demonstrate that all populations are at risk. Additionally, both short-term heat exposure and whole-pregnancy heat exposure increase the risk of stillbirth. A definitive threshold of effect has not been identified, as most studies define exposure as above the 90th centile of the usual temperature for that population. Therefore, the association between heat and stillbirth has been found with exposures from as low as >12.64°C up to >46.4°C. The pathophysiological pathways by which maternal heat exposure may lead to stillbirth, based on human and animal studies, include both placental and embryonic or fetal impacts. Although evidence gaps remain and further research is needed to characterise these mechanistic pathways in more detail, preliminary evidence suggests epigenetic changes, alteration in imprinted genes, congenital abnormalities, reduction in placental blood flow, size and function all play a part. Finally, we explore this topic from a public health perspective; we discuss and evaluate the current public health guidance on minimising the risk of extreme heat in the community. There is limited pregnancy-specific guidance within heatwave planning, and no evidence-based interventions have been established to prevent poor pregnancy outcomes. We highlight priority research questions to move forward in the field and specifically note the urgent need for evidence-based interventions that are sustainable.
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Affiliation(s)
- Ana Bonell
- Medical Research Council Unit The Gambia at London School of Hygiene and Tropical Medicine, Fajara, The Gambia
- Centre on Climate Change and Planetary Health, London School of Hygiene and Tropical Medicine, London, UK
| | - Cherie Part
- Centre on Climate Change and Planetary Health, London School of Hygiene and Tropical Medicine, London, UK
| | - Uduak Okomo
- Medical Research Council Unit The Gambia at London School of Hygiene and Tropical Medicine, Fajara, The Gambia
| | - Rebecca Cole
- Centre on Climate Change and Planetary Health, London School of Hygiene and Tropical Medicine, London, UK
| | - Shakoor Hajat
- Centre on Climate Change and Planetary Health, London School of Hygiene and Tropical Medicine, London, UK
| | - Sari Kovats
- Centre on Climate Change and Planetary Health, London School of Hygiene and Tropical Medicine, London, UK
| | - Amanda N Sferruzzi-Perri
- Department of Physiology, Development and Neuroscience, Centre for Trophoblast Research, University of Cambridge, Cambridge, UK
| | - Jane E Hirst
- Nuffield Department of Women's and Reproductive Health, University of Oxford, Oxford, UK
- The George Institute for Global Health, Imperial College London, London, UK
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8
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Bonell A, Sonko B, Badjie J, Samateh T, Saidy T, Sosseh F, Sallah Y, Bajo K, Murray KA, Hirst J, Vicedo-Cabrera A, Prentice AM, Maxwell NS, Haines A. Environmental heat stress on maternal physiology and fetal blood flow in pregnant subsistence farmers in The Gambia, west Africa: an observational cohort study. Lancet Planet Health 2022; 6:e968-e976. [PMID: 36495891 PMCID: PMC9756110 DOI: 10.1016/s2542-5196(22)00242-x] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Revised: 09/12/2022] [Accepted: 09/27/2022] [Indexed: 06/17/2023]
Abstract
BACKGROUND Anthropogenic climate change has caused extreme temperatures worldwide, with data showing that sub-Saharan Africa is especially vulnerable to these changes. In sub-Saharan Africa, women comprise 50% of the agricultural workforce, often working throughout pregnancy despite heat exposure increasing the risk of adverse birth outcomes. In this study, we aimed to improve understanding of the pathophysiological mechanisms responsible for the adverse health outcomes resulting from environmental heat stress in pregnant subsistence farmers. We also aimed to provide data to establish whether environmental heat stress also has physiological effects on the fetus. METHODS We conducted an observational cohort study in West Kiang, The Gambia, at the field station for the Medical Research Council Unit The Gambia at London School of Hygiene & Tropical Medicine (named the MRC Keneba field station). Pregnant women who were aged 16 years or older and who were at <36 weeks' gestation of any gravida or parity were invited to participate in the study. Participants were eligible if they were involved in agricultural or related manual daily tasks of living. Participants were ineligible if they refused to provide consent, had multiple pregnancies (eg, if they had twins), were acutely unwell, or were diagnosed with pre-eclampsia or eclampsia. Heat stress was measured by wet bulb globe temperature (WBGT) and by using the universal thermal climate index (UTCI), and maternal heat strain was directly measured by modified physiological strain index calculated from heart rate and skin temperature. Outcome measures of fetal heart rate (FHR) and fetal strain (defined as a FHR >160 beats per min [bpm] or <115 bpm, or increase in umbilical artery resistance index) were measured at rest and during the working period. Multivariable repeated measure models (linear regression for FHR, and logistic regression for fetal strain) were used to evaluate the association of heat stress and heat strain with acute fetal strain. FINDINGS Between Aug 26, 2019, and March 27, 2020, 92 eligible participants were recruited to the study. Extreme heat exposure was frequent, with average exposures of WBGT of 27·2°C (SD 3·6°C) and UTCI equivalent temperature of 34·0°C (SD 3·7°C). The total effect of UTCI on fetal strain resulted in an odds ratio (OR) of 1·17 (95% CI 1·09-1·29; p<0·0001), with an adjusted direct effect of OR of 1·12 (1·03-1·21; p=0·010) with each 1°C increase in UTCI. The adjusted OR of maternal heat strain on fetal strain was 1·20 (1·01-1·43; p=0·038), using the UTCI model, with each unit increase. INTERPRETATION Data from our study show that decreasing maternal exposure to heat stress and heat strain is likely to reduce fetal strain, with the potential to reduce adverse birth outcomes. Further work that explores the association between heat stress and pregnancy outcomes in a variety of settings and populations is urgently needed to develop effective interventions. FUNDING The Wellcome Trust.
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Affiliation(s)
- Ana Bonell
- Medical Research Unit The Gambia at London School of Hygiene & Tropical Medicine, Fajara, The Gambia; Centre on Climate Change and Planetary Health, London School of Hygiene & Tropical Medicine, London, UK.
| | - Bakary Sonko
- Medical Research Unit The Gambia at London School of Hygiene & Tropical Medicine, Fajara, The Gambia
| | - Jainaba Badjie
- Medical Research Unit The Gambia at London School of Hygiene & Tropical Medicine, Fajara, The Gambia
| | - Tida Samateh
- Medical Research Unit The Gambia at London School of Hygiene & Tropical Medicine, Fajara, The Gambia
| | - Tida Saidy
- Medical Research Unit The Gambia at London School of Hygiene & Tropical Medicine, Fajara, The Gambia
| | - Fatou Sosseh
- Medical Research Unit The Gambia at London School of Hygiene & Tropical Medicine, Fajara, The Gambia
| | - Yahya Sallah
- Medical Research Unit The Gambia at London School of Hygiene & Tropical Medicine, Fajara, The Gambia
| | - Kebba Bajo
- Medical Research Unit The Gambia at London School of Hygiene & Tropical Medicine, Fajara, The Gambia
| | - Kris A Murray
- Medical Research Unit The Gambia at London School of Hygiene & Tropical Medicine, Fajara, The Gambia; Centre on Climate Change and Planetary Health, London School of Hygiene & Tropical Medicine, London, UK; MRC Centre for Global Infectious Disease Analysis, School of Public Health, Imperial College London, London, UK
| | - Jane Hirst
- Nuffield Department of Women's and Reproductive Health and the George Institute for Global Health, University of Oxford, Oxford, UK
| | - Ana Vicedo-Cabrera
- Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland; Oeschger Center for Climate Change Research, University of Bern, Bern, Switzerland
| | - Andrew M Prentice
- Medical Research Unit The Gambia at London School of Hygiene & Tropical Medicine, Fajara, The Gambia
| | - Neil S Maxwell
- Environmental Extremes Laboratory, University of Brighton, Eastbourne, UK
| | - Andy Haines
- Centre on Climate Change and Planetary Health, London School of Hygiene & Tropical Medicine, London, UK
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9
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Malaspina D. Editorial for Special Issue: From cytokines to climate and C-sections and from micronutrients to the microbiome: Neurodevelopment and the risk for psychosis. Schizophr Res 2022; 247:1-6. [PMID: 35396142 DOI: 10.1016/j.schres.2022.02.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2022] [Revised: 02/06/2022] [Accepted: 02/07/2022] [Indexed: 11/28/2022]
Affiliation(s)
- Dolores Malaspina
- Icahn School of Medicine at Mount Sinai, Departments of Psychiatry, Neuroscience, Genetic and Genomic Sciences, New York, N.Y. , U.S.A..
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10
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Puthota J, Alatorre A, Walsh S, Clemente JC, Malaspina D, Spicer J. Prenatal ambient temperature and risk for schizophrenia. Schizophr Res 2022; 247:67-83. [PMID: 34620533 PMCID: PMC8977400 DOI: 10.1016/j.schres.2021.09.020] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Revised: 09/20/2021] [Accepted: 09/22/2021] [Indexed: 11/21/2022]
Abstract
OBJECTIVE We conducted a systematic review of the published literature to test the hypothesis that maternal exposure to extremes of ambient temperatures during pregnancy is associated with the risk for psychiatric disorders or congenital malformations in offspring, both of which are indicative of perturbations of fetal neurodevelopment. METHOD This study was conducted in accordance with the recommendations outlined in the Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting proposal. Electronic databases (Ovid MEDLINE, Ovid Embase, Ovid PsycINFO, Ovid Global Health, Web of Science, and Cochrane Library) were searched. Four independent reviewers selected studies with the following criteria: (1) prenatal maternal ambient temperature exposure; (2) outcome of offspring psychiatric disorder or congenital defects; (3) empirical study; (4) full-length article, no conference presentations or abstracts. RESULTS Twenty-two studies met criteria and one was added from a reference list (n = 23). Of these, schizophrenia (n = 5), anorexia nervosa (n = 3) and congenital cardiovascular malformations (n = 6) studies were the most common. Each of these categories showed some evidence of association with an early pregnancy maternal ambient heat exposure effect, with other evidence for a late pregnancy cold effect. CONCLUSION Some evidence supports a role for early pregnancy maternal exposure to extreme ambient heat in the development of psychiatric disorders, but large-scale, prospective cohort data on individual births is essential. Optimal studies will be conducted in seasonally variable climates, accounting for actual maternal residence over the pregnancy and at parturition, local environmental temperature records, and appropriate covariates, similar to studies identified by this systematic review for congenital malformations.
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Affiliation(s)
| | - Andrea Alatorre
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai, United States of America
| | - Samantha Walsh
- Levy Library, Icahn School of Medicine at Mount Sinai, United States of America
| | - Jose C Clemente
- Department of Genetics & Genomic Sciences, Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, United States of America
| | - Dolores Malaspina
- Departments of Psychiatry, Neuroscience, Genetics & Genomics, Icahn School of Medicine at Mount Sinai, United States of America
| | - Julie Spicer
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai, United States of America.
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11
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L’Heveder A, Chan M, Mitra A, Kasaven L, Saso S, Prior T, Pollock N, Dooley M, Joash K, Jones BP. Sports Obstetrics: Implications of Pregnancy in Elite Sportswomen, a Narrative Review. J Clin Med 2022; 11:jcm11174977. [PMID: 36078907 PMCID: PMC9456821 DOI: 10.3390/jcm11174977] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2022] [Revised: 08/01/2022] [Accepted: 08/09/2022] [Indexed: 11/16/2022] Open
Abstract
Increasing numbers of females are participating in elite sports, with a record number having competed at the Tokyo Olympic Games. Importantly, the ages of peak performance and fertility are very likely to coincide; as such, it is inevitable that pregnancy will occur during training and competition. Whilst there is considerable evidence to promote regular exercise in pregnancy, with benefits including a reduction in hypertensive disorders, gestational diabetes, and reduced rates of post-natal depression, few studies have been conducted which include elite athletes. Indeed, there are concerns that high-intensity exercise may lead to increased rates of miscarriage and preterm labour, amongst other pregnancy-related complications. There is minimal guidance on the obstetric management of athletes, and consequently, healthcare professionals frequently adopt a very conservative approach to managing such people. This narrative review summarises the evidence on the antenatal, intrapartum, and postpartum outcomes in elite athletes and provides recommendations for healthcare providers, demonstrating that generally, pregnant athletes can continue their training, with a few notable exceptions. It also summarises the physiological changes that occur in pregnancy and reviews the literature base regarding how these changes may impact performance, with benefits arising from pregnancy-associated cardiovascular adaptations at earlier gestations but later changes causing an increased risk of injury and fatigue.
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Affiliation(s)
- Ariadne L’Heveder
- Department of Surgery & Cancer, Imperial College London, London W12 0NN, UK
- Correspondence: ; Tel.: +44-07989356191
| | - Maxine Chan
- Department of Surgery & Cancer, Imperial College London, London W12 0NN, UK
- Queen Charlotte’s and Chelsea Hospital, Imperial College NHS Trust, Du Cane Road, London W12 0HS, UK
| | - Anita Mitra
- Department of Surgery & Cancer, Imperial College London, London W12 0NN, UK
- Queen Charlotte’s and Chelsea Hospital, Imperial College NHS Trust, Du Cane Road, London W12 0HS, UK
| | - Lorraine Kasaven
- Department of Surgery & Cancer, Imperial College London, London W12 0NN, UK
- Queen Charlotte’s and Chelsea Hospital, Imperial College NHS Trust, Du Cane Road, London W12 0HS, UK
| | - Srdjan Saso
- Department of Surgery & Cancer, Imperial College London, London W12 0NN, UK
- Queen Charlotte’s and Chelsea Hospital, Imperial College NHS Trust, Du Cane Road, London W12 0HS, UK
| | - Tomas Prior
- Queen Charlotte’s and Chelsea Hospital, Imperial College NHS Trust, Du Cane Road, London W12 0HS, UK
| | - Noel Pollock
- Institute of Sport, Exercise & Health, University College London, London W1T 7HA, UK
- British Athletics, National Performance Institute, Loughborough, LE11 3TU, UK
| | | | - Karen Joash
- Queen Charlotte’s and Chelsea Hospital, Imperial College NHS Trust, Du Cane Road, London W12 0HS, UK
| | - Benjamin P. Jones
- Department of Surgery & Cancer, Imperial College London, London W12 0NN, UK
- Queen Charlotte’s and Chelsea Hospital, Imperial College NHS Trust, Du Cane Road, London W12 0HS, UK
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12
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El Nahla S, Abdul-Mughni A, Dessouki A, Hassan S. Effect of the Prenatal Exposure of Khat on the Skeleton of Developing Rabbit Embryo: Morphometric and Gross Anatomical Study. Fetal Pediatr Pathol 2022; 41:381-395. [PMID: 33026921 DOI: 10.1080/15513815.2020.1827319] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
Background: Khat leaves are chewed by many people worldwide, mainly in Africa and the southwest Arabian peninsula. Materials and methods: 27 apparently healthy adult New Zealand rabbits (3 males & 24 females) of 2.5 ± 0.5 kg body weight were used in this work. The animals were divided into 4 groups (control, low, medium and high doses groups). The khat extract was administered orally during (8th -18th) day of gestation. The mothers were sacrificed on the 29th day of gestation. The skeletons of the fetuses were stained with Alizarin Red S and Alcian Blue. Results: Skeletal examination of the fetuses of treated dams showed several types of malformations and variations in all treated groups such as unossified phalanges, deformed sternum, completely unossified vertebral lamina and opened anterior and posterior fontanelles, and reduced length of limb long bones. Conclusion: These findings support the teratogenic effect of the khat on the developing rabbit fetus.
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Affiliation(s)
- Sanaa El Nahla
- Department of Anatomy and Embryology, Faculty of Veterinary Medicine, Suez Canal University, Ismailia Egypt
| | - Aref Abdul-Mughni
- Department of Anatomy and Embryology, Faculty of Agriculture and Veterinary Medicine, Dhamar University, Dhamar Yemen
| | - Amina Dessouki
- Department of Pathology, Faculty of Veterinary Medicine, Suez Canal University, Ismailia Egypt
| | - Said Hassan
- Department of Anatomy and Embryology, Faculty of Veterinary Medicine, Suez Canal University, Ismailia Egypt
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13
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Selzer EB, Blain D, Hufnagel RB, Lupo PJ, Mitchell LE, Brooks BP. Review of Evidence for Environmental Causes of Uveal Coloboma. Surv Ophthalmol 2021; 67:1031-1047. [PMID: 34979194 DOI: 10.1016/j.survophthal.2021.12.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Revised: 12/22/2021] [Accepted: 12/27/2021] [Indexed: 10/19/2022]
Abstract
Uveal coloboma is a condition defined by missing ocular tissues and is a significant cause of childhood blindness. It occurs from a failure of the optic fissure to close during embryonic development,and may lead to missing parts of the iris, ciliary body, retina, choroid, and optic nerve. Because there is no treatment for coloboma, efforts have focused on prevention. While several genetic causes of coloboma have been identified, little definitive research exists regarding the environmental causes of this condition. We review the current literature on environmental factors associated with coloboma in an effort to guide future research and preventative counseling related to this condition.
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Affiliation(s)
- Evan B Selzer
- Ophthalmic Genetics & Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, MD
| | - Delphine Blain
- Ophthalmic Genetics & Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, MD
| | - Robert B Hufnagel
- Ophthalmic Genetics & Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, MD
| | - Philip J Lupo
- Department of Pediatrics, Section of Hematology-Oncology, Baylor College of Medicine, Houston, TX
| | - Laura E Mitchell
- Department of Epidemiology, Human Genetics and Environmental Sciences, UTHealth School of Public Health, Houston, TX
| | - Brian P Brooks
- Ophthalmic Genetics & Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, MD.
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14
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Ganguly S, Margel S. Design of Magnetic Hydrogels for Hyperthermia and Drug Delivery. Polymers (Basel) 2021; 13:4259. [PMID: 34883761 PMCID: PMC8659876 DOI: 10.3390/polym13234259] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2021] [Revised: 11/30/2021] [Accepted: 12/02/2021] [Indexed: 12/28/2022] Open
Abstract
Hydrogels are spatially organized hydrophilic polymeric systems that exhibit unique features in hydrated conditions. Among the hydrogel family, composite hydrogels are a special class that are defined as filler-containing systems with some tailor-made properties. The composite hydrogel family includes magnetic-nanoparticle-integrated hydrogels. Magnetic hydrogels (MHGs) show magneto-responsiveness, which is observed when they are placed in a magnetic field (static or oscillating). Because of their tunable porosity and internal morphology they can be used in several biomedical applications, especially diffusion-related smart devices. External stimuli may influence physical and chemical changes in these hydrogels, particularly in terms of volume and shape morphing. One of the most significant external stimuli for hydrogels is a magnetic field. This review embraces a brief overview of the fabrication of MHGs and two of their usages in the biomedical area: drug delivery and hyperthermia-based anti-cancer activity. As for the saturation magnetization imposed on composite MHGs, they are easily heated in the presence of an alternating magnetic field and the temperature increment is dependent on the magnetic nanoparticle concentration and exposure time. Herein, we also discuss the mode of different therapies based on non-contact hyperthermia heating.
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Affiliation(s)
- Sayan Ganguly
- Bar-Ilan Institute for Nanotechnology and Advanced Materials, Department of Chemistry, Bar-Ilan University, Ramat-Gan 52900, Israel
| | - Shlomo Margel
- Bar-Ilan Institute for Nanotechnology and Advanced Materials, Department of Chemistry, Bar-Ilan University, Ramat-Gan 52900, Israel
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15
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Antoun S, Ellul P, Peyre H, Rosenzwajg M, Gressens P, Klatzmann D, Delorme R. Fever during pregnancy as a risk factor for neurodevelopmental disorders: results from a systematic review and meta-analysis. Mol Autism 2021; 12:60. [PMID: 34537069 PMCID: PMC8449704 DOI: 10.1186/s13229-021-00464-4] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Accepted: 08/06/2021] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND Fever during pregnancy is a relatively common and most often trivial event. However, under specific conditions, it could affect significantly fetal brain development. Few studies, with inconsistent results, investigated whether fever, regardless the pathogen, could represent a risk factor for neurodevelopmental disorders (NDD) in the offspring. We aimed to explore further this question by performing a systematic review and meta-analysis. METHODS Peer-reviewed studies exploring the occurrence of NDD in offspring after a fetal exposure to maternal fever were included. We specifically considered the impact of fever severity and duration, taking into consideration some confounding variables such as the use of antipyretic during pregnancy, the trimester in which the fever arose, the maternal age or smoking at time of gestation. MEDLINE, EMBASE, PsycINFO, Cochrane and Web of Science were searched without language restriction. PRISMA recommendations were followed. Odds ratio (OR) were pooled using random-effects meta-analysis. Heterogeneity in effect size across studies was studied using random-effects meta-regression analysis. (PROSPERO CRD42020182801). RESULTS We finally considered ten studies gathering a total of 10,304 children with NDD. Among them, 1394 were exposed to fever during pregnancy. The selected studies were divided into 5 case-control studies and 5 cohort studies. Maternal exposure to fever during pregnancy increased the risk of NDD in offspring with an OR of 1.24 [95% CI: 1.12-1.38]. Secondary analysis revealed an increased risk for NDD when fever occurred during the first trimester of gestation [OR 1.13-95% CI: 1.02-1.26]. LIMITATIONS We excluded studies that considered infections with no evidence of fever. Another potential limitation may be the possible heterogeneity between study designs (cohorts and case-control). CONCLUSION Additional evidence supported the association between fever during pregnancy and increased risk for NDD in offspring. Careful monitoring should be considered for children born from mothers with a febrile episode during pregnancy (specifically during the first trimester).
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Affiliation(s)
- Stephanie Antoun
- Child and Adolescent Psychiatry Department, Robert Debré Hospital, APHP, Paris University, Paris, France
| | - Pierre Ellul
- Child and Adolescent Psychiatry Department, Robert Debré Hospital, APHP, Paris University, Paris, France
- Immunology-Immunopathology-Immunotherapy (i3), INSERM U959, Sorbonne University, Paris, France
| | - Hugo Peyre
- Child and Adolescent Psychiatry Department, Robert Debré Hospital, APHP, Paris University, Paris, France
- Université de Paris, Inserm UMR, 1141 NeuroDiderot, Paris, France
| | - Michelle Rosenzwajg
- Immunology-Immunopathology-Immunotherapy (i3), INSERM U959, Sorbonne University, Paris, France
| | - Pierre Gressens
- Université de Paris, Inserm UMR, 1141 NeuroDiderot, Paris, France
- Centre for the Developing Brain, Division of Imaging Sciences and Biomedical Engineering, King’s College London, King’s Health Partners, St. Thomas’ Hospital, London, UK
| | - David Klatzmann
- Immunology-Immunopathology-Immunotherapy (i3), INSERM U959, Sorbonne University, Paris, France
| | - Richard Delorme
- Child and Adolescent Psychiatry Department, Robert Debré Hospital, APHP, Paris University, Paris, France
- Human Genetics and Cognitive Functions, Institut Pasteur, Paris, France
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16
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Vilcins D, Baker P, Jagals P, Sly PD. The Association of Ambient Temperature with Extremely Preterm Births. Matern Child Health J 2021; 25:1638-1645. [PMID: 34387796 DOI: 10.1007/s10995-021-03203-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/07/2021] [Indexed: 12/01/2022]
Abstract
INTRODUCTION Extremely preterm births (EPT), require complex decision making and significant medical interventions. While environmental factors such as ambient temperature extremes have been associated with preterm births, little is known of the environmental associations with EPT births. The objective of this study is to explore whether ambient temperature is associated with increased risk of EPT birth. METHODS Birth records for 315,226 infants born in Queensland Australia (2007-2015) were matched to average maximum and minimum temperature for the last month of pregnancy. Odds ratios and 95% confidence intervals were calculated using a generalised linear model. Population attributable risk was calculated for a 5% reduction in maximum temperature. RESULTS Each one degree increase in maximum [aOR 1.03 (95% CI 1.01, 1.05)] and minimum temperature [aOR 1.02 (95% CI 1.01, 1.04)] was associated with an increase in odds for EPT birth. Increased odds for EPT births was found for maternal smoking [aOR 1.46 (95% CI 1.23, 1.72)], increasing plurality [OR 6.38 (95% CI 5.48, 7.42)] and stillbirth [aOR 342.99 (95% CI 295.53, 398.06)]. When stratified by birth status, the association was only found for live births. DISCUSSION Higher temperatures are associated with small increases in the odds of delivering an infant in the EPT period. The risk may be enhanced for women who smoke during pregnancy. Women at an increased risk of preterm births should be counselled around methods to reduce their exposure to excessive heat.
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Affiliation(s)
- Dwan Vilcins
- Children's Health and Environment Program, Child Health Research Centre, The University of Queensland, Brisbane, Australia.
- Children's Health and Environment Program, L7 Centre for Children's Health Research, 62 Graham St, South Brisbane, QLD, 4101, Australia.
| | - Peter Baker
- School of Public Health, The University of Queensland, Brisbane, Australia
| | - Paul Jagals
- Children's Health and Environment Program, Child Health Research Centre, The University of Queensland, Brisbane, Australia
| | - Peter D Sly
- Children's Health and Environment Program, Child Health Research Centre, The University of Queensland, Brisbane, Australia
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17
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Tioleco N, Silberman AE, Stratigos K, Banerjee-Basu S, Spann MN, Whitaker AH, Turner JB. Prenatal maternal infection and risk for autism in offspring: A meta-analysis. Autism Res 2021; 14:1296-1316. [PMID: 33720503 DOI: 10.1002/aur.2499] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2020] [Revised: 02/13/2021] [Accepted: 02/21/2021] [Indexed: 12/27/2022]
Abstract
While prenatal maternal infection has received attention as a preventable and treatable risk factor for autism, findings have been inconsistent. This paper presents the results of a meta-analysis to determine whether the weight of the evidence supports such an association. Studies with a categorical diagnosis of autism as the outcome and an assessment of its association with prenatal maternal infection or fever (or the data necessary to compute this association) were included. A total of 36 studies met these criteria. Two independent reviewers extracted data on study design, methods of assessment, type of infectious agent, site of infection, trimester of exposure, definition of autism, and effect size. Analyses demonstrated a statistically significant association of maternal infection/fever with autism in offspring (OR = 1.32; 95% CI = 1.20-1.46). Adjustment for evident publication bias slightly weakened this association. There was little variation in effect sizes across agent or site of infection. Small differences across trimester of exposure were not statistically significant. There was some evidence that recall bias associated with status on the outcome variable leads to differential misclassification of exposure status. Nonetheless, the overall association is only modestly reduced when studies potentially contaminated by such bias are removed. Although causality has not been firmly established, these findings suggest maternal infection during pregnancy confers an increase in risk for autism in offspring. Given the prevalence of this risk factor, it is possible that the incidence of autism would be reduced by 12%-17% if maternal infections could be prevented or safely treated in a timely manner. LAY SUMMARY: This study is a meta-analysis of the association of maternal infection during pregnancy and subsequent autism in offspring. In combining the results from 36 studies of this association we find that a significant relationship is present. The association does not vary much across the types of infections or when they occur during pregnancy. We conclude that the incidence of autism could be substantially reduced if maternal infections could be prevented or safely treated in a timely manner.
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Affiliation(s)
- Nina Tioleco
- Division of Child and Adolescent Psychiatry, Columbia University Irving Medical Center, New York, New York, USA.,Division of Child and Adolescent Psychiatry, The New York State Psychiatric Institute, New York, New York, USA
| | - Anna E Silberman
- Division of Child and Adolescent Psychiatry, The New York State Psychiatric Institute, New York, New York, USA
| | - Katharine Stratigos
- Division of Child and Adolescent Psychiatry, Columbia University Irving Medical Center, New York, New York, USA
| | | | - Marisa N Spann
- Department of Psychiatry and Pediatrics, Columbia University Irving Medical Center, New York, New York, USA
| | - Agnes H Whitaker
- Division of Child and Adolescent Psychiatry, Columbia University Irving Medical Center, New York, New York, USA.,Division of Child and Adolescent Psychiatry, The New York State Psychiatric Institute, New York, New York, USA
| | - J Blake Turner
- Division of Child and Adolescent Psychiatry, Columbia University Irving Medical Center, New York, New York, USA.,Division of Child and Adolescent Psychiatry, The New York State Psychiatric Institute, New York, New York, USA
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18
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Jee B, Dhar R, Singh S, Karmakar S. Heat Shock Proteins and Their Role in Pregnancy: Redefining the Function of "Old Rum in a New Bottle". Front Cell Dev Biol 2021; 9:648463. [PMID: 33996811 PMCID: PMC8116900 DOI: 10.3389/fcell.2021.648463] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Accepted: 04/06/2021] [Indexed: 12/18/2022] Open
Abstract
Pregnancy in humans is a multi-step complex physiological process comprising three discrete events, decidualization, implantation and placentation. Its overall success depends on the incremental advantage that each of the preceding stages passes on to the next. The success of these synchronized sequels of events is an outcome of timely coordination between them. The pregnancy events are coordinated and governed primarily by the ovarian steroid hormones, estrogen and progesterone, which are essentially ligand-activated transcription factors. It's well known that intercellular signaling of steroid hormones engages a plethora of adapter proteins that participate in executing the biological functions. This involves binding of the hormone receptor complex to the DNA response elements in a sequence specific manner. Working with Drosophila melanogaster, the heat shock proteins (HSPs) were originally described by Ferruccio Ritossa back in the early 1960s. Over the years, there has been considerable advancement of our understanding of these conserved families of proteins, particularly in pregnancy. Accumulating evidence suggests that endometrial and uterine cells have an abundance of HSP27, HSP60, HSP70 and HSP90, implying their possible involvement during the pregnancy process. HSPs have been found to be associated with decidualization, implantation and placentation, with their dysregulation associated with implantation failure, pregnancy loss and other feto-maternal complications. Furthermore, HSP is also associated with stress response, specifically in modulating the ER stress, a critical determinant for reproductive success. Recent advances suggest a therapeutic role of HSPs proteins in improving the pregnancy outcome. In this review, we summarized our latest understanding of the role of different members of the HSP families during pregnancy and associated complications based on experimental and clinical evidences, thereby redefining and exploring their novel function with new perspective, beyond their prototype role as molecular chaperones.
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Affiliation(s)
- Babban Jee
- Department of Health Research, Ministry of Health and Family Welfare, Government of India, New Delhi, India
| | - Ruby Dhar
- Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India
| | - Sunil Singh
- Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India
| | - Subhradip Karmakar
- Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India
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Effects of Environmental Conditions on Nephron Number: Modeling Maternal Disease and Epigenetic Regulation in Renal Development. Int J Mol Sci 2021; 22:ijms22084157. [PMID: 33923831 PMCID: PMC8073167 DOI: 10.3390/ijms22084157] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2021] [Revised: 04/08/2021] [Accepted: 04/15/2021] [Indexed: 12/14/2022] Open
Abstract
A growing body of evidence suggests that low nephron numbers at birth can increase the risk of chronic kidney disease or hypertension later in life. Environmental stressors, such as maternal malnutrition, medication and smoking, can influence renal size at birth. Using metanephric organ cultures to model single-variable environmental conditions, models of maternal disease were evaluated for patterns of developmental impairment. While hyperthermia had limited effects on renal development, fetal iron deficiency was associated with severe impairment of renal growth and nephrogenesis with an all-proximal phenotype. Culturing kidney explants under high glucose conditions led to cellular and transcriptomic changes resembling human diabetic nephropathy. Short-term high glucose culture conditions were sufficient for long-term alterations in DNA methylation-associated epigenetic memory. Finally, the role of epigenetic modifiers in renal development was tested using a small compound library. Among the selected epigenetic inhibitors, various compounds elicited an effect on renal growth, such as HDAC (entinostat, TH39), histone demethylase (deferasirox, deferoxamine) and histone methyltransferase (cyproheptadine) inhibitors. Thus, metanephric organ cultures provide a valuable system for studying metabolic conditions and a tool for screening for epigenetic modifiers in renal development.
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20
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In utero heat stress alters postnatal phenotypes in swine. Theriogenology 2020; 154:110-119. [PMID: 32540511 DOI: 10.1016/j.theriogenology.2020.05.013] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Revised: 05/05/2020] [Accepted: 05/10/2020] [Indexed: 12/12/2022]
Abstract
The prenatal environment influences offspring health and development, and this is readily apparent when considering the well-described effects of maternal nutrition and stress on the postnatal metabolism, neural function, and stress response of progeny. Moreover, in laboratory species, sheep, and humans, the effects of in utero heat stress on offspring development have been described in detail for >50 years. Despite our extensive knowledge of the postnatal phenotypes elicited by in utero stressors, the carryover effects of in utero heat stress in pigs have only recently begun to be elucidated. The effects of climate change on increasing global temperatures, combined with greater metabolic heat production in modern swine, has increased heat stress susceptibility in pigs. Greater heat stress susceptibility can negatively affect swine welfare and performance and may impact future generations of pigs through in utero heat stress. Pigs exposed to in utero heat stress develop a variety of postnatal phenotypes that prevent profitable production, and compromise health, and welfare in commercial production systems. Specifically, in utero heat stress alters the postnatal stress response, core body temperature, response to an immune challenge, and is teratogenic. In addition, in utero heat stress changes postnatal body composition through reduced lean and increased adipose tissue accretion rates, respectively. Furthermore, in utero heat stress reduces piglet birth weight, body weight gain, and reproductive efficiency. Although the economic impact of in utero heat stress in pigs has yet to be determined, it likely rivals the postnatal consequences of heat stress and is a threat to the global sustainability of swine production.
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Bonell A, Hirst J, Vicedo-Cabrera AM, Haines A, Prentice AM, Maxwell NS. A protocol for an observational cohort study of heat strain and its effect on fetal wellbeing in pregnant farmers in The Gambia. Wellcome Open Res 2020; 5:32. [PMID: 32292825 PMCID: PMC7141168 DOI: 10.12688/wellcomeopenres.15731.2] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/26/2020] [Indexed: 11/20/2022] Open
Abstract
Introduction: Climate change predictions indicate that global temperatures are likely to exceed those seen in the last 200,000 years, rising by around 4°C above pre-industrial levels by 2100 (without effective mitigation of current emission rates). In regions of the world set to experience extreme temperatures, women often work outside in agriculture even during pregnancy. The implications of heat strain in pregnancy on maternal health and pregnancy outcome are not well understood. This protocol describes a study to assess the physiological response of pregnant women to environmental heat stress and the immediate effect this has on fetal wellbeing. Methods and analysis: The study will be performed in West Kiang district, The Gambia; a semi-arid zone in West Africa with daily maximum temperatures ranging from approximately 32 to 40°C. We will recruit 125 pregnant women of all ages who perform agricultural work during their pregnancy. Participants will be followed every two months until delivery. At each study visit fetal growth will be measured by ultrasound scan. During the course of their working day we will take the following measurements: continuous maternal physiological measurements (heart rate, respiratory rate, chest skin temperature and tri-axis accelerometer data); intermittent maternal tympanic core temperature, four point skin temperature, blood pressure; intermittent fetal heart rate and, if eligible, umbilical artery doppler; intermittent environmental measurements of air temperature, humidity, solar radiation and wind speed. Venous blood and urine will be collected at beginning and end of day for biomarkers of heat strain or fetal distress and hydration status.
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Affiliation(s)
- Ana Bonell
- Medical Research Council Gambia @ London School of Hygiene and Tropical Medicine, Fajara, The Gambia
| | - Jane Hirst
- Nuffield Department of Women's and Reproductive Health and the George Institute for Global Health, University of Oxford, Oxford, UK
| | - Ana M Vicedo-Cabrera
- Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.,Oeschger Center for Climate Change Research, University of Bern, Bern, Switzerland
| | - Andy Haines
- Department of Public Health, Environment and Society; Department of Population health, London School of Hygiene and Tropical Medicine, London, UK
| | - Andrew M Prentice
- Medical Research Council Gambia @ London School of Hygiene and Tropical Medicine, Fajara, The Gambia
| | - Neil S Maxwell
- Environmental Extremes Laboratory, University of Brighton, Brighton, UK
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Bonell A, Hirst J, Vicedo-Cabrera AM, Haines A, Prentice AM, Maxwell NS. A protocol for an observational cohort study of heat strain and its effect on fetal wellbeing in pregnant farmers in The Gambia. Wellcome Open Res 2020; 5:32. [PMID: 32292825 PMCID: PMC7141168 DOI: 10.12688/wellcomeopenres.15731.1] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/26/2020] [Indexed: 11/15/2023] Open
Abstract
Introduction: Climate change predictions indicate that global temperatures are likely to exceed those seen in the last 200,000 years, rising by around 4°C above pre-industrial levels by 2100 (without effective mitigation of current emission rates). In regions of the world set to experience extreme temperatures, women often work outside in agriculture even during pregnancy. The implications of heat strain in pregnancy on maternal health and pregnancy outcome are not well understood. This protocol describes a study to assess the physiological response of pregnant women to environmental heat stress and the immediate effect this has on fetal wellbeing. Methods and analysis: The study will be performed in West Kiang district, The Gambia; a semi-arid zone in West Africa with daily maximum temperatures ranging from approximately 32 to 40°C. We will recruit 125 pregnant women of all ages who perform agricultural work during their pregnancy. Participants will be followed every two months until delivery. At each study visit fetal growth will be measured by ultrasound scan. During the course of their working day we will take the following measurements: continuous maternal physiological measurements (heart rate, respiratory rate, chest skin temperature and tri-axis accelerometer data); intermittent maternal tympanic core temperature, four point skin temperature, blood pressure; intermittent fetal heart rate and, if eligible, umbilical artery doppler; intermittent environmental measurements of air temperature, humidity, solar radiation and wind speed. Venous blood and urine will be collected at beginning and end of day for biomarkers of heat strain or fetal distress and hydration status.
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Affiliation(s)
- Ana Bonell
- Medical Research Council Gambia @ London School of Hygiene and Tropical Medicine, Fajara, The Gambia
| | - Jane Hirst
- Nuffield Department of Women's and Reproductive Health and the George Institute for Global Health, University of Oxford, Oxford, UK
| | - Ana M. Vicedo-Cabrera
- Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland
- Oeschger Center for Climate Change Research, University of Bern, Bern, Switzerland
| | - Andy Haines
- Department of Public Health, Environment and Society; Department of Population health, London School of Hygiene and Tropical Medicine, London, UK
| | - Andrew M. Prentice
- Medical Research Council Gambia @ London School of Hygiene and Tropical Medicine, Fajara, The Gambia
| | - Neil S. Maxwell
- Environmental Extremes Laboratory, University of Brighton, Brighton, UK
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Maternal fever during pregnancy and offspring attention deficit hyperactivity disorder. Sci Rep 2019; 9:9519. [PMID: 31266998 PMCID: PMC6606630 DOI: 10.1038/s41598-019-45920-7] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2018] [Accepted: 06/17/2019] [Indexed: 01/09/2023] Open
Abstract
Maternal fever during pregnancy is associated with several adverse child outcomes. We investigated associations between maternal fever and ADHD among offspring, as well as the sub-dimensions of ADHD - inattention and hyperactivity/impulsivity. Data came from the Norwegian Mother and Child Cohort Study, including more than 114,000 children. Information about children’s ADHD diagnoses was obtained from the Norwegian Patient Register. Mothers reported on inattention and hyperactivity/impulsivity symptoms in questionnaires at 8 years. Logistic regression analysis showed that children exposed to maternal fever in the first trimester received an ADHD diagnosis more often than unexposed children (Odds Ratio (OR) = 1.31, 95% confidence interval (CI) = 1.06–1.61). For children exposed twice or more in the first trimester, the OR was 2.64 (CI = 1.36–5.14). Linear regression analysis showed elevated inattention symptoms among children exposed to fever in the first (Cohen’s d = 0.09, CI = 0.03–0.15) and second (Cohen’s d = 0.05, CI = 0.01–0.09) trimester. Results were similar whether the mother had taken acetaminophen for their fever or not. Hyperactivity/impulsivity symptoms were not related to maternal fever. The results indicate that maternal fever in early pregnancy may be a risk factor for ADHD, and particularly for inattention problems. This risk is neither mitigated nor inflated by use of acetaminophen.
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The etiology of congenital scoliosis: genetic vs. environmental—a report of three monozygotic twin cases. EUROPEAN SPINE JOURNAL : OFFICIAL PUBLICATION OF THE EUROPEAN SPINE SOCIETY, THE EUROPEAN SPINAL DEFORMITY SOCIETY, AND THE EUROPEAN SECTION OF THE CERVICAL SPINE RESEARCH SOCIETY 2018; 27:533-537. [DOI: 10.1007/s00586-018-5604-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/11/2018] [Accepted: 04/12/2018] [Indexed: 10/17/2022]
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Ravanelli N, Casasola W, English T, Edwards KM, Jay O. Heat stress and fetal risk. Environmental limits for exercise and passive heat stress during pregnancy: a systematic review with best evidence synthesis. Br J Sports Med 2018; 53:799-805. [PMID: 29496695 DOI: 10.1136/bjsports-2017-097914] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/05/2018] [Indexed: 11/03/2022]
Abstract
OBJECTIVE Pregnant women are advised to avoid heat stress (eg, excessive exercise and/or heat exposure) due to the risk of teratogenicity associated with maternal hyperthermia; defined as a core temperature (Tcore) ≥39.0°C. However, guidelines are ambiguous in terms of critical combinations of climate and activity to avoid and may therefore unnecessarily discourage physical activity during pregnancy. Thus, the primary aim was to assess Tcore elevations with different characteristics defining exercise and passive heat stress (intensity, mode, ambient conditions, duration) during pregnancy relative to the critical maternal Tcore of ≥39.0°C. DESIGN Systematic review with best evidence synthesis. DATA SOURCES EMBASE, MEDLINE, SCOPUS, CINAHL and Web of Science were searched from inception to 12 July 2017. STUDY ELIGIBILITY CRITERIA Studies reporting the Tcore response of pregnant women, at any period of gestation, to exercise or passive heat stress, were included. RESULTS 12 studies satisfied our inclusion criteria (n=347). No woman exceeded a Tcore of 39.0°C. The highest Tcore was 38.9°C, reported during land-based exercise. The highest mean end-trial Tcore was 38.3°C (95% CI 37.7°C to 38.9°C) for land-based exercise, 37.5°C (95% CI 37.3°C to 37.7°C) for water immersion exercise, 36.9°C (95% CI 36.8°C to 37.0°C) for hot water bathing and 37.6°C (95% CI 37.5°C to 37.7°C) for sauna exposure. CONCLUSION The highest individual core temperature reported was 38.9°C. Immediately after exercise (either land based or water immersion), the highest mean core temperature was 38.3°C; 0.7°C below the proposed teratogenic threshold. Pregnant women can safely engage in: (1) exercise for up to 35 min at 80%-90% of their maximum heart rate in 25°C and 45% relative humidity (RH); (2) water immersion (≤33.4°C) exercise for up to 45 min; and (3) sitting in hot baths (40°C) or hot/dry saunas (70°C; 15% RH) for up to 20 min, irrespective of pregnancy stage, without reaching a core temperature exceeding the teratogenic threshold.
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Affiliation(s)
- Nicholas Ravanelli
- Thermal Ergonomics Laboratory, Faculty of Health Sciences, University of Sydney, Sydney, New South Wales, Australia.,School of Human Kinetics, University of Ottawa, Ottawa, Ontario, Canada
| | - William Casasola
- Thermal Ergonomics Laboratory, Faculty of Health Sciences, University of Sydney, Sydney, New South Wales, Australia.,Exeter Medical School, University of Exeter, Exeter, UK
| | - Timothy English
- Thermal Ergonomics Laboratory, Faculty of Health Sciences, University of Sydney, Sydney, New South Wales, Australia
| | - Kate M Edwards
- Charles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia
| | - Ollie Jay
- Thermal Ergonomics Laboratory, Faculty of Health Sciences, University of Sydney, Sydney, New South Wales, Australia.,School of Human Kinetics, University of Ottawa, Ottawa, Ontario, Canada.,Charles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia
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Hutson MR, Keyte AL, Hernández-Morales M, Gibbs E, Kupchinsky ZA, Argyridis I, Erwin KN, Pegram K, Kneifel M, Rosenberg PB, Matak P, Xie L, Grandl J, Davis EE, Katsanis N, Liu C, Benner EJ. Temperature-activated ion channels in neural crest cells confer maternal fever-associated birth defects. Sci Signal 2017; 10:10/500/eaal4055. [PMID: 29018170 DOI: 10.1126/scisignal.aal4055] [Citation(s) in RCA: 51] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Birth defects of the heart and face are common, and most have no known genetic cause, suggesting a role for environmental factors. Maternal fever during the first trimester is an environmental risk factor linked to these defects. Neural crest cells are precursor populations essential to the development of both at-risk tissues. We report that two heat-activated transient receptor potential (TRP) ion channels, TRPV1 and TRPV4, were present in neural crest cells during critical windows of heart and face development. TRPV1 antagonists protected against the development of hyperthermia-induced defects in chick embryos. Treatment with chemical agonists of TRPV1 or TRPV4 replicated hyperthermia-induced birth defects in chick and zebrafish embryos. To test whether transient TRPV channel permeability in neural crest cells was sufficient to induce these defects, we engineered iron-binding modifications to TRPV1 and TRPV4 that enabled remote and noninvasive activation of these channels in specific cellular locations and at specific developmental times in chick embryos with radio-frequency electromagnetic fields. Transient stimulation of radio frequency-controlled TRP channels in neural crest cells replicated fever-associated defects in developing chick embryos. Our data provide a previously undescribed mechanism for congenital defects, whereby hyperthermia activates ion channels that negatively affect fetal development.
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Affiliation(s)
- Mary R Hutson
- Division of Neonatology, Department of Pediatrics, Duke University Medical Center, Jean and George Brumley, Jr. Neonatal-Perinatal Institute, Durham, NC 27710, USA
| | - Anna L Keyte
- Division of Neonatology, Department of Pediatrics, Duke University Medical Center, Jean and George Brumley, Jr. Neonatal-Perinatal Institute, Durham, NC 27710, USA.,Brain Imaging and Analysis Center, Duke University School of Medicine, Durham, NC 27710, USA.,Department of Radiology, Duke University School of Medicine, Durham, NC 27710, USA
| | - Miriam Hernández-Morales
- Brain Imaging and Analysis Center, Duke University School of Medicine, Durham, NC 27710, USA.,Department of Radiology, Duke University School of Medicine, Durham, NC 27710, USA.,Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, CA 94720, USA.,Helen Wills Neuroscience Institute, University of California, Berkeley, CA 94720, USA
| | - Eric Gibbs
- Brain Imaging and Analysis Center, Duke University School of Medicine, Durham, NC 27710, USA.,Department of Radiology, Duke University School of Medicine, Durham, NC 27710, USA
| | - Zachary A Kupchinsky
- Center for Human Disease Modeling, Duke University Medical Center, Durham, NC 27710, USA
| | - Ioannis Argyridis
- Brain Imaging and Analysis Center, Duke University School of Medicine, Durham, NC 27710, USA.,Department of Radiology, Duke University School of Medicine, Durham, NC 27710, USA
| | - Kyle N Erwin
- Division of Neonatology, Department of Pediatrics, Duke University Medical Center, Jean and George Brumley, Jr. Neonatal-Perinatal Institute, Durham, NC 27710, USA
| | - Kelly Pegram
- Division of Neonatology, Department of Pediatrics, Duke University Medical Center, Jean and George Brumley, Jr. Neonatal-Perinatal Institute, Durham, NC 27710, USA
| | - Margaret Kneifel
- Brain Imaging and Analysis Center, Duke University School of Medicine, Durham, NC 27710, USA.,Department of Radiology, Duke University School of Medicine, Durham, NC 27710, USA
| | - Paul B Rosenberg
- Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA
| | - Pavle Matak
- Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27710, USA
| | - Luke Xie
- Brain Imaging and Analysis Center, Duke University School of Medicine, Durham, NC 27710, USA.,Department of Radiology, Duke University School of Medicine, Durham, NC 27710, USA
| | - Jörg Grandl
- Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA
| | - Erica E Davis
- Center for Human Disease Modeling, Duke University Medical Center, Durham, NC 27710, USA
| | - Nicholas Katsanis
- Center for Human Disease Modeling, Duke University Medical Center, Durham, NC 27710, USA
| | - Chunlei Liu
- Brain Imaging and Analysis Center, Duke University School of Medicine, Durham, NC 27710, USA. .,Department of Radiology, Duke University School of Medicine, Durham, NC 27710, USA.,Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, CA 94720, USA.,Helen Wills Neuroscience Institute, University of California, Berkeley, CA 94720, USA
| | - Eric J Benner
- Division of Neonatology, Department of Pediatrics, Duke University Medical Center, Jean and George Brumley, Jr. Neonatal-Perinatal Institute, Durham, NC 27710, USA.
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27
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Quality and Safety of Obstetric Practices Using New Modalities— Ultrasound, MR, and CT. Clin Obstet Gynecol 2017; 60:546-561. [DOI: 10.1097/grf.0000000000000300] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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Crews SM, McCleery WT, Hutson MS. Pathway to a phenocopy: Heat stress effects in early embryogenesis. Dev Dyn 2015; 245:402-13. [PMID: 26498920 DOI: 10.1002/dvdy.24360] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2015] [Revised: 10/09/2015] [Accepted: 10/13/2015] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Heat shocks applied at the onset of gastrulation in early Drosophila embryos frequently lead to phenocopies of U-shaped mutants-having characteristic failures in the late morphogenetic processes of germband retraction and dorsal closure. The pathway from nonspecific heat stress to phenocopied abnormalities is unknown. RESULTS Drosophila embryos subjected to 30-min, 38 °C heat shocks at gastrulation appear to recover and restart morphogenesis. Post-heat-shock development appears normal, albeit slower, until a large fraction of embryos develop amnioserosa holes (diameters > 100 µm). These holes are positively correlated with terminal U-shaped phenocopies. They initiate between amnioserosa cells and open over tens of minutes by evading normal wound healing responses. They are not caused by tissue-wide increases in mechanical stress or decreases in cell-cell adhesion, but instead appear to initiate from isolated apoptosis of amnioserosa cells. CONCLUSIONS The pathway from heat shock to U-shaped phenocopies involves the opening of one or more large holes in the amnioserosa that compromise its structural integrity and lead to failures in morphogenetic processes that rely on amnioserosa-generated tensile forces. The proposed mechanism by which heat shock leads to hole initiation and expansion is heterochonicity, i.e., disruption of morphogenetic coordination between embryonic and extra-embryonic cell types.
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Affiliation(s)
- Sarah M Crews
- Department of Physics and Astronomy, Vanderbilt University, Nashville, Tennessee
| | - W Tyler McCleery
- Department of Physics and Astronomy, Vanderbilt University, Nashville, Tennessee
| | - M Shane Hutson
- Department of Physics and Astronomy, Vanderbilt University, Nashville, Tennessee.,Vanderbilt Institute for Integrative Biosystem Research and Education, Vanderbilt University, Nashville, Tennessee
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Congenital heart defects and maternal fever: systematic review and meta-analysis. J Perinatol 2014; 34:677-82. [PMID: 24811224 DOI: 10.1038/jp.2014.76] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2013] [Revised: 02/27/2014] [Accepted: 03/13/2014] [Indexed: 11/08/2022]
Abstract
OBJECTIVE To systematically review and meta-analyze the relation between maternal fever in the first trimester and congenital heart defect (CHD) in offspring. STUDY DESIGN We searched PubMed (1977-2012), Embase (1974-2012) and the Cochrane Library (2012) databases to identify relevant articles. Random effects model were performed, with the conduction of subgroup analysis. RESULT Meta-analysis yielded a pooled odds ratio of 1.53 (95% confidence interval=1.36 to 1.73) for the magnitude of the relation between maternal fever in the first trimester and CHD in offspring. As to subgroup analysis, it is associated with ventricular septal defects (VSDs) and right obstructive defects. CONCLUSION Our analysis suggests that maternal fever in the first trimester is the risk factor of congenital heart diseases in offspring. Through the subgroup analysis, we find that exposure to maternal fever is the risk factor of VSD and right obstructive defects.
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Zhang H, Yang Z, Cui G. Anencephalic monocephalic conjoined twins detected by sonography. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2014; 33:547-551. [PMID: 24567469 DOI: 10.7863/ultra.33.3.549] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/03/2023]
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Dreier JW, Andersen AMN, Berg-Beckhoff G. Systematic review and meta-analyses: fever in pregnancy and health impacts in the offspring. Pediatrics 2014; 133:e674-88. [PMID: 24567014 DOI: 10.1542/peds.2013-3205] [Citation(s) in RCA: 110] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND AND OBJECTIVE Fever during pregnancy has been suspected to harm the developing fetus. However, until now, no systematic analysis of the available evidence has been undertaken to assess the impact of maternal fever on health outcomes in the child. The goal of this study was to systematically review evidence from epidemiologic studies on adverse health outcomes of the offspring in relation to exposure to maternal fever during pregnancy. METHODS Systematic searches in PubMed, Web of Science, and the Cochrane Library were performed by using Medical Subject Headings, Boolean operators, and truncation, and references of references were reviewed. Cohort and case-control studies addressing health outcomes of prenatal fever exposure in humans were eligible for inclusion. Studies with no direct reference to fever, studies in selected populations (eg, preterm births), and studies published before 1990 were excluded. RESULTS The available literature supported an increased risk of adverse offspring health in association with fever during pregnancy. The strongest evidence was available for neural tube defects, congenital heart defects, and oral clefts, in which meta-analyses suggested between a 1.5- and nearly 3-fold increased risk with fever exposure in the first trimester. We did not find strong evidence of a dose-response relationship, but there was some evidence that antipyretic medications may have a protective effect when used in relation to febrile episodes. CONCLUSIONS We found substantial evidence to support the contention that maternal fever during pregnancy may negatively affect offspring health. The harmful effects seemed to cover both short- and longer-term health outcomes; however, for several outcomes, the evidence was insufficient to judge any association.
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Miller MW, Church CC. Arrhenius thermodynamics and birth defects: chemical teratogen synergy. Untested, testable, and projected relevance. ACTA ACUST UNITED AC 2014; 99:50-60. [PMID: 23723172 DOI: 10.1002/bdrc.21025] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2012] [Accepted: 11/25/2012] [Indexed: 11/10/2022]
Abstract
This article addresses the issue of hyperthermia-induced birth defects with an accompanying additional teratogen, be it a chemical or a physical agent (i.e., a simultaneous "combinational" exposure to two teratogens, one of which is hyperthermia). Hyperthermia per se is a recognized human and animal teratogen. An excellent example of such combinational exposures is an epileptic woman who becomes pregnant while taking valproic acid (VPA) to control seizures. VPA is a recognized chemical teratogen, and fever (hyperthermia) is not an uncommon event during pregnancy. While VPA also may occasionally induce fever as a side effect, we are concerned here with fevers arising from other, unrelated causes. There is a small but internally consistent literature on these combinational-teratogen exposures involving hyperthermia plus a chemical teratogen; in each instance, the effect level has been observed to be synergistically elevated above levels induced by the separate teratogenic components. The data were empirical. The observed synergy is, however, consistent with Arrhenius thermodynamics, a well-known chemical rate equation. The need for information about combinational teratogen exposures is acute; fever is a common occurrence during pregnancy; and there are many instances whereby there is also the simultaneous presence of some other teratogen(s). Given that the rate of autism spectrum disorders in the United States was recently presented as 1 in 88 births, it seems reasonable to suspect that such combinational regimens are much more prevalent than previously thought. Our hypothesis is that synergistic birth defect levels from combinational regimens are consistent with Arrhenius thermodynamics.
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Affiliation(s)
- Morton W Miller
- University of Rochester Medical Center, School of Medicine and Dentistry, Department of Obstetrics & Gynecology, New York, 14642-8668, USA.
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Sim KB, Lee JY, Phi JH, Kim SK, Wang KC. Experimental models of spinal open neural tube defect and Chiari type II malformation. Childs Nerv Syst 2013; 29:1435-49. [PMID: 24013317 DOI: 10.1007/s00381-013-2148-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2013] [Accepted: 05/02/2013] [Indexed: 10/26/2022]
Abstract
INTRODUCTION Experimental animal models are essential for investigation of the pathoembryogenesis, pathophysiology, and management strategy of spinal open neural tube defect (ONTD) and its associated anomalies including Chiari type II malformation. Genetic, chemical/nutrient, and surgical models have been widely used for a variety of purposes. The aim of this article is to review the representative animal models of spinal ONTD and associated Chiari type II malformation with respect to their advantages and disadvantages. DISCUSSION Among them, the surgical model was described in detail because it is familiar to neurosurgeons and it is used for evaluations of prenatal repair of spinal ONTDs. The surgical model also has advantages because it allows quantitative analysis of the lesions. A description of our previous studies on spinal ONTDs using a chick surgical model is presented as an example.
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Affiliation(s)
- Ki-Bum Sim
- Department of Neurosurgery, Jeju National University College of Medicine, Jeju, South Korea
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Giampietro PF, Dunwoodie SL, Kusumi K, Pourquié O, Tassy O, Offiah AC, Cornier AS, Alman BA, Blank RD, Raggio CL, Glurich I, Turnpenny PD. Molecular diagnosis of vertebral segmentation disorders in humans. ACTA ACUST UNITED AC 2013; 2:1107-21. [PMID: 23496422 DOI: 10.1517/17530059.2.10.1107] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
BACKGROUND Vertebral malformations contribute substantially to the pathophysiology of kyphosis and scoliosis, common health problems associated with back and neck pain, disability, cosmetic disfigurement and functional distress. OBJECTIVE To provide an overview of the current understanding of vertebral malformations, at both the clinical level and the molecular level, and factors that contribute to their occurrence. METHODS The literature related to the following was reviewed: recent advances in the understanding of the molecular embryology underlying vertebral development and relevance to elucidation of etiologies of several known human vertebral malformation syndromes; outcomes of molecular studies elucidating genetic contributions to congenital and sporadic vertebral malformations; and complex interrelationships between genetic and environmental factors that contribute to the pathogenesis of isolated syndromic and non-syndromic congenital vertebral malformations. RESULTS/CONCLUSION Expert opinions extend to discussion of the importance of establishing improved classification systems for vertebral malformation, future directions in molecular and genetic research approaches to vertebral malformation and translational value of research efforts to clinical management and genetic counseling of affected individuals and their families.
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Affiliation(s)
- Philip F Giampietro
- Marshfield Clinic, Department of Genetic Services, 1000 N. Oak Avenue, Marshfield, WI 54449, USA +1 715 221 7410 ; +1 715 389 4399 ;
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Voss M, Asbach P, Hilger A. Vertebral Anomaly in Fossil Sea Cows (Mammalia, Sirenia). Anat Rec (Hoboken) 2011; 294:980-6. [DOI: 10.1002/ar.21397] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2010] [Accepted: 03/18/2011] [Indexed: 11/06/2022]
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40
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Gucev ZS, Tasic V, Pop-Jordanova N, Sparrow DB, Dunwoodie SL, Ellard S, Young E, Turnpenny PD. Autosomal dominant spondylocostal dysostosis in three generations of a Macedonian family: Negative mutation analysis of DLL3, MESP2, HES7, and LFNG. Am J Med Genet A 2010; 152A:1378-82. [PMID: 20503311 DOI: 10.1002/ajmg.a.33471] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
The spondylocostal dysostoses (SCDs) are a heterogeneous group of axial skeletal disorders characterized by multiple segmentation defects of the vertebrae (SDV) and abnormality of the thoracic cage with mal-aligned ribs and often a reduction in rib number. The four known monogenic forms of SCD follow autosomal recessive inheritance, have generalized SDV, a broadly symmetrical thoracic cage, and result from mutations in Notch signaling pathway genes-DLL3, MESP2, LFNG, and HES7. Autosomal dominant (AD) SCD has been reported less often, is very variable, and molecular genetic mechanisms remain elusive. Here, we report a three-generation, non-consanguineous family with four affected individuals demonstrating multiple or generalized SDV. Scoliosis was present and the trunk shortened but the ribs were relatively mildly affected. There were no other significant organ abnormalities, no obvious dysmorphic features, neurodevelopment was normal, and all investigations, including mutation analysis of DLL3, MESP2, LFNG, and HES7, were normal. A non-pathogenic variant was detected in LFNG but it did not segregate with the phenotype. This Macedonian kindred adds to knowledge of AD SCD and to our knowledge is the first to be tested for the four Notch pathway genes known to be associated with SCD.
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Affiliation(s)
- Zoran S Gucev
- Medical Faculty Skopje, Divizija BB, Skopje, Macedonia.
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Torchinsky A, Toder V. Mechanisms of the embryo's response to embryopathic stressors: a focus on p53. J Reprod Immunol 2010; 85:76-80. [PMID: 20227113 DOI: 10.1016/j.jri.2010.01.003] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2009] [Revised: 12/08/2009] [Accepted: 01/22/2010] [Indexed: 10/19/2022]
Abstract
Whether the embryo develops normally or not depends not only on the mechanisms regulating embryonic development, but also on the mechanisms acting to resist and repair injures in the embryo due to harmful maternal stimuli or exposure to developmental toxicants. The key role of p53 in the regulation of the embryo's response to embryopathic stress inducing DNA damage is beyond doubt. Yet, the question why p53 in some cases acts as a suppressor of teratogenesis, whereas in other cases it induces teratogenesis, remains unanswered. In this minireview we analyze studies in which organogenesis-stage embryos were exposed to various developmental toxicants and suggest a model unifying the teratogenesis-suppressing and teratogenesis-promoting role of p53. This model predicts that p53 protects embryos from developmental toxicant inducing oxidative stress and promotes the process of maldevelopment induced by developmental toxicants activating apoptotic machinery. Certainly, many questions must be answered before concluding the extent to which this model is correct. Yet, it does allow us to explain some discrepancies obtained in studies performed to date. Also, the model might be useful in choosing molecular targets for further studies addressing p53-controlled and p53-independent mechanisms, which determine the embryo's resistance to embryopathic stress.
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Affiliation(s)
- Arkady Torchinsky
- Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv, 69978, Israel.
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Ács N, Bánhidy F, Puhó EH, Czeizel AE. A possible association between acute infectious diarrhoea in pregnant women and congenital abnormalities in their offspring—a population-based case–control study. ACTA ACUST UNITED AC 2010; 42:359-67. [DOI: 10.3109/00365540903499415] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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Houston LE, Odibo AO, Macones GA. The safety of obstetrical ultrasound: a review. Prenat Diagn 2009; 29:1204-12. [DOI: 10.1002/pd.2392] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
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Schneider‐Kolsky ME, Ayobi Z, Lombardo P, Brown D, Kedang B, Gibbs ME. Ultrasound exposure of the foetal chick brain: effects on learning and memory. Int J Dev Neurosci 2009; 27:677-83. [DOI: 10.1016/j.ijdevneu.2009.07.007] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2009] [Revised: 07/14/2009] [Accepted: 07/29/2009] [Indexed: 11/15/2022] Open
Affiliation(s)
- Michal E. Schneider‐Kolsky
- Department of Medical Imaging & Radiation SciencesSchool of Biomedical ScienceFaculty of Medicine, Nursing and Health SciencesMonash UniversityClayton3800VictoriaAustralia
| | - Zohel Ayobi
- Department of Anatomy & Developmental BiologySchool of Biomedical ScienceFaculty of Medicine, Nursing and Health SciencesMonash UniversityClayton3800VictoriaAustralia
| | - Paul Lombardo
- Department of Medical Imaging & Radiation SciencesSchool of Biomedical ScienceFaculty of Medicine, Nursing and Health SciencesMonash UniversityClayton3800VictoriaAustralia
| | - Damian Brown
- Department of Medical Imaging & Radiation SciencesSchool of Biomedical ScienceFaculty of Medicine, Nursing and Health SciencesMonash UniversityClayton3800VictoriaAustralia
| | - Ben Kedang
- Department of Medical Imaging & Radiation SciencesSchool of Biomedical ScienceFaculty of Medicine, Nursing and Health SciencesMonash UniversityClayton3800VictoriaAustralia
| | - Marie E. Gibbs
- Department of Anatomy & Developmental BiologySchool of Biomedical ScienceFaculty of Medicine, Nursing and Health SciencesMonash UniversityClayton3800VictoriaAustralia
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Abstract
STUDY DESIGN Literature review. OBJECTIVE To provide a current overview of congenital scoliosis and associated conditions. SUMMARY OF BACKGROUND DATA The etiology of congenital scoliosis is unknown. A variety of factors have been implicated in the development of vertebral abnormalities. These factors provide clues to the origin of congenital scoliosis. METHODS A search of PubMed, using the keywords congenital scoliosis, etiology, and genetics was performed. RESULTS Environmental factors, genetics, vitamin deficiency, chemicals, and drugs, singly or in combination, have all been implicated in the development of vertebral abnormalities. Whatever the cause, the physiologic injury occurs early in the embryologic period, well before the development of cartilage and bone. The resulting defects can lead to full or partial fusion or lack of development of the vertebrae, which, in turn, can cause a curvature that, may be progressive during the growth of the child. CONCLUSION The origin of congenital scoliosis may be environmental, genetic, or a combination of factors. Research on these various factors continues. Early identification and management of concomitant defects can improve the patient's quality of life.
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Barrier M, Dix DJ, Mirkes PE. Inducible 70 kDa heat shock proteins protect embryos from teratogen-induced exencephaly: Analysis using Hspa1a/a1b knockout mice. ACTA ACUST UNITED AC 2009; 85:732-40. [DOI: 10.1002/bdra.20610] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
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Savion S, Sofer M, Brengauz-Breitmann M, Fein A, Torchinsky A, Toder V. NF-κB regulates the response of embryonic cells to heat shock. Int J Hyperthermia 2009; 23:277-86. [PMID: 17523020 DOI: 10.1080/02656730701297546] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022] Open
Abstract
NF-kappaB was shown previously to regulate apoptotic cell death processes in various experimental systems. However, its role in controlling teratogen-induced cell death has not been established yet. Therefore, the objective of the present study was to explore the involvement of the p65 subunit of NF-kappaB in the response of mouse embryonic fibroblasts (MEFs) to heat shock, using p65 knockout (p65-/-) cells. Indeed, we found p65-/- MEFs to be more susceptible to the exposure to heat shock, as compared with wild-type (WT) MEFs, as they demonstrated a more prominent decrease in cell survival and proliferation as well as the appearance of cells undergoing apoptotic cell death. These heat-shock-induced effects were preceded by a decrease in p65 expression in WT cells, which was accompanied by a decrease in IkappaBalpha expression in WT MEFs, while disappearing completely in p65-/- MEFs and accordingly, by an increase in p-IkappaBalpha expression in both cell lines, which was found to be more prominent in p65-/- MEFs. Interestingly, the heat shock-induced decrease in p65 expression was accompanied by an increase in HSP70 expression in both cell lines. However, it was again found to be more prominent in p65-/- MEFs. Taken together, our results suggest a protective role for the p65 subunit of NF-kappaB in mechanisms underlying the response of embryonic cells to heat shock.
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Affiliation(s)
- S Savion
- Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Israel.
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Qing Y, Yingmao G, Shaoling L. IDENTIFICATION AND VALIDATION OF DIFFERENTIALLY EXPRESSED GENES IN NEURAL TUBE DEFECTS OF GOLDEN HAMSTER INDUCED BY HYPERTHERMIA USING SUPPRESSION SUBTRACTIVE HYBRIDIZATION. Int J Neurosci 2009; 117:1193-208. [PMID: 17613121 DOI: 10.1080/00207450600934903] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
Hyperthermia during early pregnancy can induce neural tube defects (NTD) in embryos. In order to identify the differentially expressed genes that participate in this pathologic course, the authors performed suppression subtractive hybridization in two directions: forward and reverse. Neural tube tissues from golden hamster of normal and hyperthermia groups are used as the samples. As a result, several down-regulated genes were revealed and according to the function of their protein products they were classified into four categories: ribosomal proteins, metabolic enzymes, transcription and translation related factors, and others. On the other hand, the study found that two up-regulated gene fractions were of the same sequence and homology analysis shows that they are homologous to phosphoglycerate kinase 1 (pgk1). Of all these genes, differential expression patterns were confirmed by Northern blot analysis. The study results show that the genes identified have different expression and are stongly related to NTD induced by hyperthermia.
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Affiliation(s)
- Yang Qing
- Histology and Embryology Institution, Medical School of Shandong University, Jinan, China
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Paquette LB, Jackson HA, Tavaré CJ, Miller DA, Panigrahy A. In utero eye development documented by fetal MR imaging. AJNR Am J Neuroradiol 2009; 30:1787-91. [PMID: 19541779 DOI: 10.3174/ajnr.a1664] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
BACKGROUND AND PURPOSE To date, very limited attention has been given to ocular abnormalities or growth parameters detected by fetal MR imaging. Our objective was to retrospectively determine the relationship between different parameters of eye development and estimated gestational age in the human fetus by use of fetal MR imaging. MATERIALS AND METHODS A retrospective study was performed to measure the transverse diameter, interocular distance, and lens diameter of the globes of 127 fetuses who had a morphologically normal central nervous system. Multiple single-shot T2 fast spin-echo images were obtained with a 1.5T magnet by use of contiguous 3-mm intervals in at least 2 orthogonal planes. Loess curves were fitted to explore the relationship between gestational age and each of the 3 measurements of interest. Different models were compared statistically to determine the model of best fit. RESULTS For each variable of interest, the "best" model of eye growth was a quadratic function. Specifically, lens growth seems to plateau after 36 weeks of gestation, interocular distance plateaus after 36 weeks of gestation, and globe growth plateaus after 42 weeks of gestation. CONCLUSIONS The lens, orbit, and interocular distance growth of the fetus can be demonstrated on fetal MR imaging. All 3 measurements suggest a quadratic model of growth, which indicates slowing of growth toward the end of gestation.
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Affiliation(s)
- L B Paquette
- Division of Neonatology, Institute of Maternal and Fetal Health, Childrens Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, CA 90027, USA
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Giampietro PF, Dunwoodie SL, Kusumi K, Pourquié O, Tassy O, Offiah AC, Cornier AS, Alman BA, Blank RD, Raggio CL, Glurich I, Turnpenny PD. Progress in the understanding of the genetic etiology of vertebral segmentation disorders in humans. Ann N Y Acad Sci 2009; 1151:38-67. [PMID: 19154516 DOI: 10.1111/j.1749-6632.2008.03452.x] [Citation(s) in RCA: 52] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Vertebral malformations contribute substantially to the pathophysiology of kyphosis and scoliosis, common health problems associated with back and neck pain, disability, cosmetic disfigurement, and functional distress. This review explores (1) recent advances in the understanding of the molecular embryology underlying vertebral development and relevance to elucidation of etiologies of several known human vertebral malformation syndromes; (2) outcomes of molecular studies elucidating genetic contributions to congenital and sporadic vertebral malformation; and (3) complex interrelationships between genetic and environmental factors that contribute to the pathogenesis of isolated syndromic and nonsyndromic congenital vertebral malformation. Discussion includes exploration of the importance of establishing improved classification systems for vertebral malformation, future directions in molecular and genetic research approaches to vertebral malformation, and translational value of research efforts to clinical management and genetic counseling of affected individuals and their families.
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Affiliation(s)
- Philip F Giampietro
- Department of Medical Genetic Services, Marshfield Clinic, 1000 North Oak Avenue, Marshfield, WI 54449, USA.
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