Organism responses to environmental change require coordinated changes across correlated traits, so-called syndromes. For example, animals differ in their "pace-of-life syndrome" (POLS); suites of correlated life-history, behavioral and physiological traits. But standard "gene-centric" evolutionary theory cannot explain why POLSs exist because it assumes that the expression of phenotypic traits of animals is determined by genotype-specified reaction norms; it ignores that developmental processes can bias the direction of evolution so that phenotypes no longer match genotype-by-environment interactions. Here we apply a development-centric perspective to derive new POLS hypotheses that can resolve the conflict that current POLS predictions fail to explain which species/populations are resilient to environmental change.

The "fetal origin of adult diseases hypothesis" encompasses the notion that intrauterine growth restriction (IUGR) alters fetal development trajectories. Various neonatal metrics inform IUGR, but not all contributors to IUGR have an impact on development trajectories. Chronic IUGR (twins) and slowly varying IUGR (seasonal) have little to no effect on later life trajectories. Perhaps development trajectories may evolve through other mechanisms, as for example, multiple short-lived periods of IUGR and repeated stimulation of metabolic pathways.

Daily temperature variation could deliver a frequent IUGR as pregnant women would experience some degree of placental vasoconstriction during maximum/midday temperatures. We assessed the association with daily temperature amplitudes for globally distributed records of crude fetal growth rates (CFGR) and BMI. Paired birthweight (BW) and gestational age (GA) data permitted analyses of CFGR in 70 countries and subsequent analysis of CFGR for association with daily temperature amplitude, seasonal temperature amplitude, mean annual temperature, calorie intake per day per-1 person-1, BMI, height, and socioeconomic conditions. Analog analyses were performed for gestational age, calorie intake, BMI, and height.

CFGR and BMI showed a clear association with daily temperature amplitudes, which was not the case for gestational age, calorie intake, and height.

We show that daily temperature amplitudes are associated with both CFGR and BMI. These results permit a wider ecological appreciation of the hypothesis because daily temperature amplitudes inform environmental aridity and food scarcity. We discuss how scarcity, affluence, and the epidemiological environment influence the prevalence of afflictions associated with the fetal origin of adult disease hypothesis.

Early-life adversity influences adult fitness across vertebrate species. In polygynous systems with intense intrasexual competition, males may be more sensitive to conditions experienced during development. However, the importance of different aspects of the early-life environment and how their effects differ between the sexes remains poorly understood. Here, we used a long-term study of wild Soay sheep to characterize the early-life environment in terms of weather, infection risk, resource competition and maternal investment, and test the hypothesis that males are more vulnerable to early adversity. Birth weight, reflective of maternal investment and conditions during gestation, positively predicted lifetime breeding success in both sexes, suggesting a classic 'silver spoon' effect, though the effects were stronger in males. Males that experienced increased resource competition in their first year had lower lifetime breeding success, suggesting lasting negative consequences of nutritional stress, but there was no association in females. By contrast, challenging weather in the first winter of life was associated with stronger viability selection, with males surviving these harsh conditions having higher adult fitness. Our findings further evidence the important long-term fitness consequences of early-life adversity in wild vertebrates, demonstrating distinct aspects of the early environment may shape fitness in different and sex-specific ways.

For the survival and efficient breeding of wild-living animals, it is crucial to predict seasonal changes and prepare appropriate physiological functions and neurobehavioral mechanisms. In mammals, photoperiod serves as a reliable cue for seasonal changes in the environment, primarily transmitted by melatonin. This review focuses on the seasonal adaptation of mammalian development, specifically the effect of early-life photoperiod on reproductive, somatic, and neurobehavioral development in small- and large-sized mammals. Prediction of seasons through early-life photoperiod is particularly important for small mammals, which have relatively short longevity, to adjust their maximum growth and breeding ability in appropriate seasons during the birth year or the following round. Brain plasticity, as well as cognitive and emotional behaviors, are also highly modulated by early-life photoperiods for successful mating and spatial memory for foraging. This review first summarizes the basic knowledge and recent progress in the programming and epigenetic regulatory mechanisms of reproductive and neurobehavioral development in small mammals, including C57BL/6J mice, which cannot produce detectable amounts of melatonin. The review then focuses on the influence of perinatal environmental conditions or birth season on adult phenotypes in large livestock and humans. Studies have advanced on the concept of the developmental origins of health and disease (DOHaD). Evidence from large mammals suggests that the prediction of seasons is crucial for high-fitness functions over several years. Finally, this review discusses the association of the season of birth with life course physiology and diseases in humans, and the possible mechanisms.

Prenatal stress (PS) impacts early behavioral, neuroimmune, and cognitive development. Pregnant rat models have been very valuable in examining the mechanisms of such fetal programming. A pregnant sheep model of maternal stress offers the unique advantages of chronic in utero monitoring and manipulation. This chapter presents the techniques used to model single and multigenerational stress exposures and their pleiotropic effects on the offspring.

Intermittent fasting, such as during Ramadan, is prevalent among pregnant women. However, the association between Ramadan during pregnancy and offspring health along the life course has not been fully established.

Fetal programming research indicates that prenatal exposures, particularly during early pregnancy, can cause long-term structural and physiological changes that adversely affect offspring health. Our objective was to systematically identify and assess the evidence regarding Ramadan during pregnancy.

A total of 31 studies were sourced from PubMed, EMBASE, Web of Science, and EconLit. Included studies evaluated outcomes in individuals with prenatal Ramadan exposure, compared to unexposed Muslim controls. Main outcomes were birth weight, gestational length, and sex ratio in newborns; height, mortality, and cognition in children; and disabilities, chronic diseases, and human capital accumulation in adults. Each study was evaluated for risk of bias. The overall quality of evidence was appraised using the GRADE system. Random-effects meta-analyses were conducted for outcomes analyzed in at least three primary studies.

The initial search identified 2933 articles, 1208 duplicates were deleted. There were 31 publications fulfilled the eligibility criteria for the qualitative synthesis; 22 studies were included in meta-analyses. The overall quality of the evidence was low to moderate and differed by study design and outcome. Among newborns, prenatal Ramadan exposure was not associated with birth weight (mean difference (MD) -3 g (95% CI -18 to 11; I2 = 70%) or the likelihood of prematurity (percentage point difference (PPD) 0.19 (95% CI -0.11 to 0.49; I2 = 0%)). The probability that the newborn is male was reduced (PPD -0.14 (95% CI -0.28 to -0.00; I2 = 0%)). This potentially reflects sex-specific mortality rates resulting from adverse in utero circumstances. In childhood, the exposed performed slightly poorer on cognitive tests (MD -3.10% of a standard deviation (95% CI -4.61 to -1.58; I2 = 51%)). Height among the exposed was reduced, and this pattern was already visible at ages below 5 years (height-for-age z-score MD -0.03 (95% CI -0.06 to -0.00; I2 = 76%)). A qualitative literature synthesis revealed that childhood mortality rates were increased in low-income contexts. In adulthood, the prenatally exposed had an increased likelihood of hearing disabilities (odds ratio 1.26 (95% CI 1.09 to 1.45; I2 = 32%)), while sight was not affected. Other impaired outcomes included chronic diseases or their symptoms, and indicators of human capital accumulation such as home ownership (qualitative literature synthesis). The first trimester emerged as a sensitive period for long-term impacts.

Despite the need for more high-quality studies to improve the certainty of the evidence, the synthesis of existing research demonstrates that Ramadan during pregnancy is associated with adverse offspring health effects in childhood and especially adulthood, despite an absence of observable effects at birth. Not all health effects may apply to all Muslim communities, which are diverse in backgrounds and behaviors. Notably, moderating factors like daytime activity levels and dietary habits outside fasting hours have hardly been considered. It is imperative for future research to address these aspects.

PROSPERO (CRD42022325770).

Maternal depression is an increasingly recognized risk factor of child neurodevelopment difficulties. Few studies have investigated the association between the severity and duration of maternal depression and child development. We aimed to identify whether trajectories of maternal depressive symptoms from pregnancy to six months postpartum are associated with child development at eight months.

We included 988 mother-child pairs who participated in Shenzhen Birth Cohort Study, which was conducted in Shenzhen Nanshan Maternity & Child Healthcare Hospital of China. Maternal depressive symptoms were evaluated by the Edinburgh Postnatal Depression Scale (EPDS) at late pregnancy, 1, 3 and 6 months postpartum. Child emotional and behavioral development were assessed by Ages and Stages Questionnaires: Social-Emotional (ASQ-se) and Ages and Stages Questionnaires-Third Edition (ASQ-3) at aged 8 months. Latent profile analysis (LPA) was used to identify the trajectories of maternal depressive symptoms. Univariate and multivariate linear regression were conducted to explore the association between the depressive symptoms trajectories and child development.

Four trajectories of maternal depressive symptoms were identified by LPA: low (n = 597), subclinical (n = 91), moderately low and increasing (n = 246) and persistently high (54). Multivariable regression model showed that children of mothers with persistently high depressive symptoms were more likely to have lower scores in three ASQ-3 domains: fine motor (beta [95%C]): -2.30 [-4.32, -0.29], problem-solving (-3.72 [-5.81, -1.62]) and personal-social motor (-2.56 [-4.98, -0.15]), but higher ASQ-se scores (9.49 [5.09, 13.9]). Compared to children of mothers with low depressive symptoms, subclinical depressive symptoms were prediposed to having lower scores in two ASQ-3 domains: communication motor (-2.48 [-4.32, -0.64]) and gross motor (-2.35 [-4.2,-0.51]) and lower ASQ-se scores(4.86 [2.54, 7.18]).

Higher levels of maternal depression symptoms were associated with increased risk of child developmental delay, highlighting the importance of early intervention and addressing maternal depression from pregnancy through early childhood.

Developmental environmental stressors can have instructive effects on an organism's phenotype. This developmental plasticity can prepare organisms for potentially stressful future environments, circumventing detrimental effects on fitness. However, the physiological mechanisms underlying such adaptive plasticity are understudied, especially in vertebrates. We hypothesized that captive male zebra finches (Taeniopygia castanotis) exposed to a mild heat conditioning during development would acquire a persisting thermotolerance, and exhibit increased heat-shock protein (HSP) levels associated with a decrease in oxidative damage when exposed to a high-intensity stressor in adulthood. To test this, we exposed male finches to a prolonged mild heat conditioning (38°C) or control (22°C) treatment as juveniles. Then in a 2 × 2 factorial manner, these finches were exposed to a high heat stressor (42°C) or control (22°C) treatment as adults. Following the adult treatment, we collected testes and liver tissue and measured HSP70, HSP90, and HSP60 protein levels. In the testes, finches exhibited lower levels of HSP90 and HSP60 when exposed to the high heat stressor in adulthood if they were exposed to the mild heat conditioning as juveniles. In the liver, finches exposed to the high heat stressor in adulthood had reduced HSP90 and HSP60 levels, regardless of whether they were conditioned as juveniles. In some cases, elevated testes HSP60 levels were associated with increased liver oxidative damage and diminishment of a condition-dependent trait, indicating potential stress-induced tradeoffs. Our results indicate that a mild conditioning during development can have persisting effects on HSP expression and acquired thermotolerance.

Early life environments can have long-lasting effects on adult reproductive performance, but disentangling the influence of early and adult life environments on fitness is challenging, especially for long-lived species. Using a detailed dataset spanning over two centuries, we studied how both early and adult life environments impacted reproductive performance in preindustrial women. Due to a wide geographic range, agricultural production was lower in northern compared to southern parishes, and health conditions were worse in urban than rural parishes. We tested whether reproductive traits and offspring survival varied between early and adult life environments by comparing women who moved between different environments during their lifetime with those who moved parishes but remained in the same environment. Our findings reveal that urban-born women had an earlier age at first reproduction and less offspring surviving to adulthood than rural-born women. Moreover, switching from urban to rural led to increased offspring survival, while switching from rural to urban had the opposite effect. Finally, women who switched from rural to urban and from South to North had their first child at an older age compared to those who stayed in the same environment type. Our study underscores the complex and interactive effects of early and adult life environments on reproductive traits, highlighting the need to consider both when studying environmental effects on reproductive outcomes.

In this article, we examine the relations between extreme environmental harshness during childhood and personal fertility ideals in African students. The study is informed by biological models of predictive adaptive responses (PAR) for individual reproductive schedules in the context of life history theory (LHT). Following theoretical models of external and internal environmental cues, we tested whether war and starvation during childhood differentially predict African students' personal fertility ideals in terms of their desired number of children and their desired age of first parenthood. The data were collected in eight different countries from sub-Saharan Africa with an overall sample size of N = 392. Standardized effect estimates were obtained using a Bayesian approach. The results suggest that war and starvation are predictive of the desired number of children, but not of the desired age of first parenthood. Moreover, the effect estimates varied considerably between females and males, indicating possible interactions between the two independent variables depending on the students' sex. Furthermore, we found a small negative correlation between the desired number of children and the desired age of first parenthood, providing only weak support for a clustering of the two variables on a slow-fast continuum. The results are discussed in light of current models of individual life histories in humans.

AbstractAt certain intensities and durations, environmental stressors during development can result in changes in physiology that prepare organisms for future stressful conditions. Such plasticity can allow organisms to maintain good condition when confronted with a poor environment, potentially conferring an advantage in fitness. However, the physiological changes underlying these adaptive phenotypic adjustments are understudied. Using captive male zebra finches (Taeniopygia castanotis), we tested whether exposure to a prolonged mild stressor during development would adaptively modify their antioxidant enzyme expression, reducing oxidative damage when exposed to a high-intensity stressor in adulthood and allowing the maintenance of a secondary sexual trait. To do this, we exposed juvenile finches to either a prolonged mild heat stressor treatment (38°C) or a control temperature treatment (22°C). As adults, these finches were then exposed to either an acute high-intensity heat stressor treatment (42°C) or control temperature treatment (22°C). The beak color of males-a sexually selected trait-was quantified, as were oxidative stress parameters in the testes and liver tissues. We saw that the mild-heat-conditioned males had beaks with higher saturation and lower brightness at baseline in adulthood but that the changes in beak color in response to the high heat stressor varied. After exposure to the high heat stressor as adults, finches had higher levels of superoxide dismutase 1 and 2 in the testes and lower levels of lipid damage in the liver if they were also exposed to the mild heat conditioning as juveniles, indicating an adaptive phenotypic change.

AbstractDevelopmental plasticity allows organisms to increase the fit between their phenotype and their early-life environment. The extent to which such plasticity also enhances adult fitness is not well understood, however, particularly when early-life and adult environments differ substantially. Using a cross-factorial design that manipulated diet at two life stages, we examined predictions of major hypotheses-silver spoon, environmental matching, and thrifty phenotype-concerning the joint impacts of early-life and adult diets on adult morphology/display traits, survival, and reproductive allocation. Overall, results aligned with the silver spoon hypothesis, which makes several predictions based on the premise that development in poor-quality environments constrains adult performance. Males reared and bred on a low-protein diet had lower adult survivorship than other male treatment groups; females' survivorship was higher than males' and not impacted by early diet. Measures of allocation to reproduction primarily reflected breeding diet, but where natal diet impacted reproduction, results supported the silver spoon. Both sexes showed reduced expression of display traits when reared on a low-protein diet. Results accord with other studies in supporting the relevance of the silver spoon hypothesis to birds and point to significant ramifications of sex differences in early-life viability selection on the applicability/strength of silver spoon effects.

Anaerobic exercise decreases systemic pH and increases metabolic acidosis in athletes, altering the acid-base homeostasis. In addition, nutritional recommendations advising athletes to intake higher amounts of proteins and simple carbohydrates (including from sport functional supplements) could be detrimental to restoring acid-base balance. Here, this specific nutrition could be classified as an acidic diet and defined as 'Westernized athletic nutrition'. The maintenance of a chronic physiological state of low-grade metabolic acidosis produces detrimental effects on systemic health, physical performance, and inflammation. Therefore, nutrition must be capable of compensating for systemic acidosis from anaerobic exercise. The healthy gut microbiota can contribute to improving health and physical performance in athletes and, specifically, decrease the systemic acidic load through the conversion of lactate from systemic circulation to short-chain fatty acids in the proximal colon. On the contrary, microbial dysbiosis results in negative consequences for host health and physical performance because it results in a greater accumulation of systemic lactate, hydrogen ions, carbon dioxide, bacterial endotoxins, bioamines, and immunogenic compounds that are transported through the epithelia into the blood circulation. In conclusion, the systemic metabolic acidosis resulting from anaerobic exercise can be aggravated through an acidic diet, promoting chronic, low-grade metabolic acidosis in athletes. The individuality of athletic training and nutrition must take into consideration the acid-base homeostasis to modulate microbiota and adaptive physiological responses.

Prenatal maternal stress and mental health problems are known to increase risk for developmental psychopathology in offspring, yet pathways leading to risk or resiliency are poorly understood. In a quasi-experimental design, we prospectively examined associations between disaster-related prenatal stress, maternal mental health symptoms, and infant temperament outcomes. Mothers who were pregnant during Hurricane Harvey (N = 527) reported on objective hardships (e.g., loss of belongings or income, evacuation, home flooding) related to the storm and subsequent mental health symptoms (anxiety/depression, posttraumatic stress) across time. At a postpartum assessment, mothers reported on their infant's temperament (negative affect, positive affect, orienting/regulatory capacity). Greater objective hardship indirectly predicted higher levels of infant orienting/regulatory capacity through its association with increased maternal posttraumatic stress symptoms. Greater objective hardship also indirectly predicted higher levels of infant negative affect through its association with increased maternal anxiety/depression symptoms across time. Our findings suggest a psychological mechanism linking prenatal stress with specific temperamental characteristics via maternal mental health symptoms. Findings point to the importance of high-quality assessment and mental health services for vulnerable women and young children.

The objective of this study was to identify metabolic regulatory mechanisms affected by choline availability in rainbow trout (Oncorhynchus mykiss) broodstock diets associated with increased offspring growth performance. Three customized diets were formulated to have different levels of choline: (a) 0 % choline supplementation (Low Choline: 2065 ppm choline), (b) 0.6 % choline supplementation (Medium Choline: 5657 ppm choline), and (c) 1.2 % choline supplementation (High Choline: 9248 ppm choline). Six all-female rainbow trout families were fed experimental diets beginning 18 months post-hatch until spawning at 22 months post-hatch; their offspring were fed a commercial diet. Experimental broodstock diet did not affect overall choline, fatty acid, or amino acid content in the oocytes (p > 0.05), apart from tyrosine (p ≤ 0.05). Offspring body weights from the High and Low Choline diets did not differ from those in the Medium Choline diet (p > 0.05); however, family-by-diet and sire-by-diet interactions on offspring growth were detected (p ≤ 0.05). The High Choline diet did not improve growth performance in the six broodstock families at final harvest (520-days post-hatch, or dph). Numerous genes associated with muscle development and lipid metabolism were identified as affected by broodstock diet, including myosin, troponin C, and fatty acid binding proteins, which were associated with key signaling pathways of lipid metabolism, muscle cell development, muscle cell proliferation, and muscle cell differentiation. These findings indicate that supplementing broodstock diets with choline does regulate expression of genes related to growth and nutrient partitioning but does not lead to growth benefits in rainbow trout families selected for disease resistance.

Fetal exposure to prenatal stress can have significant consequences on short- and long-term health. Epigenetic mechanisms, especially DNA methylation (DNAm), are a possible process how these adverse environmental events could be biologically embedded. We evaluated candidate gene as well as epigenome-wide association studies associating prenatal stress and DNAm changes in peripheral tissues; however, most of these findings lack robust replication. Prenatal stress-associated epigenetic changes have also been linked to child health including internalizing problems, neurobehavioral outcomes and stress reactivity. Future studies should focus on refined measurement and definition of prenatal stress and its timing, ideally also incorporating genomic as well as longitudinal information. This will provide further opportunities to enhance our understanding of the biological embedding of prenatal stress exposure.

Prenatal exposure to heightened maternal inflammation has been associated with adverse neurodevelopmental outcomes, including atypical brain maturation and psychiatric illness. In mothers experiencing socioeconomic disadvantage, immune activation can be a product of the chronic stress inherent to such environmental hardship. While growing preclinical and clinical evidence has shown links between altered neonatal brain development and increased inflammatory states in utero, the potential mechanism by which socioeconomic disadvantage differentially impacts neural-immune crosstalk remains unclear. In the current study, we investigated associations between socioeconomic disadvantage, gestational inflammation, and neonatal white matter microstructure in 320 mother-infant dyads over-sampled for poverty. We analyzed maternal serum levels of four cytokines (IL-6, IL-8, IL-10, TNF-α) over the course of pregnancy in relation to offspring white matter microstructure and socioeconomic disadvantage. Higher average maternal IL-6 was associated with very low socioeconomic status (SES; INR < 200% poverty line) and lower neonatal corticospinal fractional anisotropy (FA) and lower uncinate axial diffusivity (AD). No other cytokine was associated with SES. Higher average maternal IL-10 was associated with lower FA and higher radial diffusivity (RD) in corpus callosum and corticospinal tracts, higher optic radiation RD, lower uncinate AD, and lower FA in inferior fronto-occipital fasciculus and anterior limb of internal capsule tracts. SES moderated the relationship between average maternal TNF-α levels during gestation and neonatal white matter diffusivity. When these interactions were decomposed, the patterns indicated that this association was significant and positive among very low SES neonates, whereby TNF-α was inversely and significantly associated with inferior cingulum AD. By contrast, among the more advantaged neonates (lower-to-higher SES [INR ≥ 200% poverty line]), TNF-α was positively and significantly associated with superior cingulum AD. Taken together, these findings suggest that the relationship between prenatal cytokine exposure and white matter microstructure differs as a function of SES. These patterns are consistent with a scenario where gestational inflammation's effects on white matter development diverge depending on the availability of foundational resources in utero.

To improve performance and recovery faster, athletes are advised to eat more often than usual and consume higher doses of simple carbohydrates, during and after exercise. Sports energetic supplements contain food additives, such as artificial sweeteners, emulsifiers, acidity regulators, preservatives, and salts, which could be harmful to the gut microbiota and impair the intestinal barrier function. The intestinal barrier plays a critical function in bidirectionally regulation of the selective transfer of nutrients, water, and electrolytes, while preventing at the same time, the entrance of harmful substances (selective permeability). The gut microbiota helps to the host to regulate intestinal homeostasis through metabolic, protective, and immune functions. Globally, the gut health is essential to maintain systemic homeostasis in athletes, and to ensure proper digestion, metabolization, and substrate absorption. Gastrointestinal complaints are an important cause of underperformance and dropout during endurance events. These complications are directly related to the loss of gut equilibrium, mainly linked to microbiota dysbiosis and leaky gut. In summary, athletes must be cautious with the elevated intake of ultra-processed foods and specifically those contained on sports nutrition supplements. This review points out the specific nutritional interventions that should be implemented and/or discontinued depending on individual gut functionality.

First identified in isogenic mice, metastable epialleles (MEs) are loci where the extent of DNA methylation (DNAm) is variable between individuals but correlates across tissues derived from different germ layers within a given individual. This property, termed systemic interindividual variation (SIV), is attributed to stochastic methylation establishment before germ layer differentiation. Evidence suggests that some putative human MEs are sensitive to environmental exposures in early development. In this review we introduce key concepts pertaining to human MEs, describe methods used to identify MEs in humans, and review their genomic features. We also highlight studies linking DNAm at putative human MEs to early environmental exposures and postnatal (including disease) phenotypes.

Insects are the most diverse animal group on the planet. Their success is reflected by the diversity of habitats in which they live. However, these habitats have undergone great changes in recent decades; understanding how these changes affect insect health and fitness is an important challenge for insect conservation. In this Review, we focus on the research that links the nutritional environment with infection and immune status in insects. We first discuss the research from the field of nutritional immunology, and we then investigate how factors such as intracellular and extracellular symbionts, sociality and transgenerational effects may interact with the connection between nutrition and immunity. We show that the interactions between nutrition and resistance can be highly specific to insect species and/or infection type - this is almost certainly due to the diversity of insect social interactions and life cycles, and the varied environments in which insects live. Hence, these connections cannot be easily generalised across insects. We finally suggest that other environmental aspects - such as the use of agrochemicals and climatic factors - might also influence the interaction between nutrition and resistance, and highlight how research on these is essential.

In this scoping review, we synthesize the literature on oxytocin and oxytocin receptor genetic and epigenetic variation in relationship to breastfeeding, maternal caregiving behavior, and maternal mental health.

A literature search was conducted in early 2022, and updated in 2023, utilizing the PRISMA scoping review reporting method, using the following MeSH headings and key terms: oxytocin, oxytocin receptor, genetics, epigenetics, methylation, pregnancy, postnatal, breastfeeding, lactation, mother-infant relations and perinatal outcomes. The search was conducted using PubMed, EMBASE, CINAHL, Google Scholar, SCOPUS, and the Cochrane Library. Inclusion criteria included: human literature which was peer reviewed and found in primary sources, printed in the English language. In addition, the study must have reported genetic/epigenetic data in either the oxytocin or oxytocin receptor gene (maternal or infant up to 12 months after birth) in relation to a breastfeeding, maternal caregiving behavior or a maternal mental health outcome. There was no date limitation. Four authors reviewed studies for eligibility. Data was extracted using a structured data extraction form.

A total of 23 studies met inclusion criteria for this review (breastfeeding n = 4, maternal caregiving behavior n = 7, and maternal mental health n = 16). Seventeen papers reported on oxytocin or oxytocin receptor genotype and nine reported epigenetic associations (namely DNA methylation). These totals are greater than 23, as studies reported on multiple outcomes. One paper assessed the interaction between genotype and methylation. While a number of genotype variations were reported, the single nucleotide polymorphism rs53576 on the oxytocin receptor gene was the most studied. Overall, variation in this polymorphism was related to postnatal depression symptoms. Among numerous epigenetic markers, site -934 was the most studied methylation site, and methylation status was associated with maternal depression and maternal caregiving behavior outcomes. Results suggest that early life experiences impact adult maternal caregiving behaviors and mental health outcomes, and vary based on genetic vulnerability. Breastfeeding outcomes were minimally studied.

This scoping review found that genetic and epigenetic variation at the oxytocin and oxytocin receptor genes were associated with maternal caregiving behavior and mental health, likely through complex gene and environment interactions. The findings suggest that maternal early life experiences and stress impact later caregiving behaviors and mental health in the postnatal period. The findings highlight potential pathways by which environment, experiences, and genes interact to impact maternal caregiving behavior and maternal mental health.

Mother-infant interactions during the early postnatal period are critical for infant survival and the scaffolding of infant development. Rodent models are used extensively to understand how these early social experiences influence neurobiology across the lifespan. However, methods for measuring postnatal dam-pup interactions typically involve time-consuming manual scoring, vary widely between research groups, and produce low density data that limits downstream analytical applications. To address these methodological issues, we developed the Automated Maternal Behavior during Early life in Rodents (AMBER) pipeline for quantifying home-cage maternal and mother-pup interactions using open-source machine learning tools. DeepLabCut was used to track key points on rat dams (32 points) and individual pups (9 points per pup) in postnatal day 1-10 video recordings. Pose estimation models reached key point test errors of approximately 4.1-10 mm (14.39 pixels) and 3.44-7.87 mm (11.81 pixels) depending on depth of animal in the frame averaged across all key points for dam and pups respectively. Pose estimation data and human-annotated behavior labels from 38 videos were used with Simple Behavioral Analysis (SimBA) to generate behavior classifiers for dam active nursing, passive nursing, nest attendance, licking and grooming, self-directed grooming, eating, and drinking using random forest algorithms. All classifiers had excellent performance on test frames, with F1 scores above 0.886. Performance on hold-out videos remained high for nest attendance (F1 = 0.990), active nursing (F1 = 0.828), and licking and grooming (F1 = 0.766) but was lower for eating, drinking, and self-directed grooming (F1 = 0.534-0.554). A set of 242 videos was used with AMBER and produced behavior measures in the expected range from postnatal 1-10 home-cage videos. This pipeline is a major advancement in assessing home-cage dam-pup interactions in a way that reduces experimenter burden while increasing reproducibility, reliability, and detail of data for use in developmental studies without the need for special housing systems or proprietary software.

The conditions animals experience during the early developmental stages of their lives can have critical ongoing effects on their future health, welfare, and proper development. In this paper we draw on evolutionary theory to improve our understanding of the processes of developmental programming, particularly Predictive Adaptive Responses (PAR) that serve to match offspring phenotype with predicted future environmental conditions. When these predictions fail, a mismatch occurs between offspring phenotype and the environment, which can have long-lasting health and welfare effects. Examples include metabolic diseases resulting from maternal nutrition and behavioral changes from maternal stress. An understanding of these processes and their evolutionary origins will help in identifying and providing appropriate developmental conditions to optimize offspring welfare. This serves as an example of the benefits of using evolutionary thinking within veterinary science and we suggest that in the same way that evolutionary medicine has helped our understanding of human health, the implementation of evolutionary veterinary science (EvoVetSci) could be a useful way forward for research in animal health and welfare.

The fields of biological anthropology and exercise physiology are closely related and can provide mutually beneficial insights into human performance. These fields often use similar methods and are both interested in how humans function, perform, and respond in extreme environments. However, these two fields have different perspectives, ask different questions, and work within different theoretical frameworks and timescales. Biological anthropologists and exercise physiologists can greatly benefit from working together when examining human adaptation, acclimatization, and athletic performance in the extremes of heat, cold, and high-altitude. Here we review the adaptations and acclimatizations in these three different extreme environments. We then examine how this work has informed and built upon exercise physiology research on human performance. Finally, we present an agenda for moving forward, hopefully, with these two fields working more closely together to produce innovative research that improves our holistic understanding of human performance capacities informed by evolutionary theory, modern human acclimatization, and the desire to produce immediate and direct benefits.

Maternal depressive symptoms in pregnancy may affect offspring health through prenatal programming of the hypothalamic-pituitary-adrenal (HPA) axis. The biological mechanisms that explain the associations between maternal prenatal depressive symptoms and offspring HPA axis regulation are not yet clear. This pre-registered investigation examines whether patterns of maternal depressive symptoms in pregnancy are associated with infant cortisol reactivity and whether this association is mediated by changes in placental corticotropin-releasing hormone (pCRH).

A sample of 174 pregnant women completed assessments in early, mid, and late pregnancy that included standardized measures of depressive symptoms and blood samples for pCRH. Infant cortisol reactivity was assessed at 1 and 6 months of age.

Greater increases in maternal depressive symptoms in pregnancy were associated with higher cortisol infant cortisol reactivity at 1 and 6 months. Greater increases in maternal depressive symptoms in pregnancy were associated with greater increases in pCRH from early to late pregnancy which in turn were associated with higher infant cortisol reactivity.

Increases in maternal depressive symptoms and pCRH over pregnancy may contribute to higher infant cortisol reactivity. These findings help to elucidate the prenatal biopsychosocial processes contributing to offspring HPA axis regulation early in development.

The developmental programming hypothesis proposes that adverse environmental insults during critical developmental periods increase the risk of diseases later in life. The kidneys are deemed susceptible to such a process, although the exact mechanisms remain elusive. Many factors have been reported to contribute to the developmental origin of chronic kidney diseases (CKD), among which peri-gestational nutrition has a central role, affecting kidney development and metabolism. Physiologically, the link between malnutrition, reduced glomerular numbers, and increased blood pressure is key in the developmental programming of CKD. However, recent studies regarding oxidative stress, mitochondrial dysfunction, epigenetic modifications, and metabolic changes have revealed potential novel pathways for therapeutic intervention. This review will discuss the role of imbalanced nutrition in the development of CKD.

Field studies of natural mammal populations present powerful opportunities to investigate the determinants of health and aging using fine-grained observations of known individuals across the life course. Here, we synthesize five decades of findings from one such study: the wild baboons of the Amboseli ecosystem in Kenya. First, we discuss the profound associations between early life adversity, adult social conditions, and key aging outcomes in this population, especially survival. Second, we review potential mediators of the relationship between early life adversity and survival in our population. Notably, our tests of two leading candidate mediators-social isolation and glucocorticoid levels-fail to identify a single, strong mediator of early life effects on adult survival. Instead, early adversity, social isolation, and glucocorticoids are independently linked to adult lifespans, suggesting considerable scope for mitigating the negative consequences of early life adversity. Third, we review our work on the evolutionary rationale for early life effects on mortality, which currently argues against clear predictive adaptive responses. Finally, we end by highlighting major themes emerging from the study of sociality, development, and aging in the Amboseli baboons, as well as important open questions for future work.

In many species, individuals that experience harsh conditions during development have poor health and fitness outcomes in adulthood, compared with peers that do not. These early-life contributions to inequality are often attributed to two classes of evolutionary hypotheses: Developmental Constraints (DC) models, which focus on the deleterious effects of low-quality early-life environments, and Predictive Adaptive Response (PAR) hypotheses, which emphasize the costs individuals incur when they make incorrect predictions about conditions in adulthood. Testing these hypotheses empirically is difficult for conceptual and analytical reasons. Here, we help resolve some of these difficulties by providing mathematical definitions for DC, PAR (particularly focusing on 'external' PAR) and related concepts. We propose a novel, quadratic regression-based statistical test derived from these definitions. Our simulations show that this approach markedly improves the ability to discriminate between DC and PAR hypotheses relative to the status quo approach, which uses interaction effects. Simulated data indicate that the interaction effects approach often conflates PAR with DC, while the quadratic regression approach yields high sensitivity and specificity for detecting PAR. Our results highlight the value of linking verbal and visual models to a formal mathematical treatment for understanding the developmental origins of inequitable adult outcomes. This article is part of the theme issue 'Evolutionary ecology of inequality'.

Contemporary evolutionary medicine has unified the idea of 'evolutionary mismatch', derived from the older idea of 'adaptive lag' in evolution, with ideas about the mismatch in development and physiology derived from the Developmental Origins of Health and Disease (DOHaD) paradigm. A number of publications in evolutionary medicine have tried to make this theoretical framework explicit. The integrative theory of mismatch captures how organisms track environments across space and time on multiple scales in order to maintain an adaptive match to the environment, and how failures of adaptive tracking lead to disease. In this review, we try to present this complex body of theory as clearly and simply as possible with the aim of facilitating its application in new domains. We introduce terminology, which is as far as possible consistent with earlier usage, to distinguish the different forms of mismatch. Mismatch in its modern form is a productive organizing concept that can help researchers articulate how physiology, development and evolution interact with one another and with environmental change to explain health outcomes.

The social environment is one of the primary sources of challenging stimuli that can induce a stress response in animals. It comprises both short-term and stable interactions among conspecifics (including unrelated individuals, mates, potential mates and kin). Social stress is of unique interest in the field of stress research because (1) the social domain is arguably the most complex and fluctuating component of an animal's environment; (2) stress is socially transmissible; and (3) stress can be buffered by social partners. Thus, social interactions can be both the cause and cure of stress. Here, we review the history of social stress research, and discuss social stressors and their effects on organisms across early life and adulthood. We also consider cross-generational effects. We discuss the physiological mechanisms underpinning social stressors and stress responses, as well as the potential adaptive value of responses to social stressors. Finally, we identify outstanding challenges in social stress research, and propose a framework for addressing these in future work.

The gestation when small for gestational age (SGA) is first associated with asthma is not well understood. Here, we use routinely acquired data from 10 weeks gestation to up to 28 years of age to test the hypothesis that SGA before birth is associated with an increased risk for asthma in a large population born between 1987 and 2015.

Databases were linked to produce a single database that held antenatal fetal ultrasound measurements; maternal characteristics; birth measurements; childhood anthropometric measurements at age 5 years; hospital admission data (1987-2015); and family doctor prescribing (2009-2015). Asthma admission and receipt of any asthma medications were the outcomes. Analyses related single and then multiple anthropometric measurements to asthma outcomes.

Outcome data were available for 63,930 individuals. Increased length in the first-trimester size was associated with a reduced odds ratio (OR) for asthma admission of 0.991 [0.983, 0.998] per mm increase and also a shorter time to first admission, with a hazard ratio risk of 0.987 [0.980, 0.994] per mm increase. Independent of all earlier measurements, increased height at 5 years (available in a subset of 15,760) was associated with reduced OR for an asthma admission, with OR of 0.874 [0.790, 0.967] per z score. Longitudinal measurements of weight were not related to asthma outcomes.

Longer first-trimester length is associated with more favorable asthma outcomes, and subsequently, increased height in childhood is also independently associated with more favorable asthma outcomes. Interventions that reduce SGA and encourage healthy postnatal growth might improve asthma outcomes.

Growth patterns may be indicative of underlying changes in body composition. However, few studies have assessed the association of growth and body composition in poorly resourced regions experiencing the double-burden of malnutrition exists. Thus, the aims of this study were to investigate the association of intrauterine and postnatal growth patterns with infant body composition at 2 years in a middle-income country.

Participants were from the International Atomic Energy Agency Multicentre Body Composition Reference study. Fat mass (FM), fat free mass (FFM), Fat mass index (FMI), fat free mass index (FFMI), and percentage fat mass (%FM) were measured in 113 infants (56 boys and 57 girls), from Soweto, South Africa, using deuterium dilution from 3 to 24 months. Birthweight categories were classified using the INTERGROWTH-21 standards as small (SGA), appropriate (AGA), and large-for gestational age (LGA). Stunting (> -2 SDS) was defined using the WHO child growth standards. Birthweight z-score, conditional relative weight and conditional length at 12 and 24 mo were regressed on body composition at 24 mo.

There were no sex differences in FM, FFM, FMI and FFMI between 3 and 24 mo. SGA and AGA both had significantly higher %FM than LGA at 12 mo. LGA had higher FM at 24 mo. Children with stunting had lower FM (Mean = 1.94, 95% CI; 1.63-2.31) and FFM (Mean = 5.91, 95% CI; 5.58-6.26) at 12 mo than non-stunting, while the reverse was true for FFMI (Mean = 13.3, 95% CI; 12.5-14.2) at 6 mo. Birthweight and conditionals explained over 70% of the variance in FM. CRW at both 12 and 24 mo was positively associated with FM and FMI. CRW at 12 mo was also positively associated with FMI, while CH at 24 mo was negatively associated with both FFMI and FMI in boys.

Both LGA and SGA were associated with higher body fat suggesting that both are disadvantaged nutritional states, likely to increase the risk of obesity. Growth patterns through infancy and toddler period (1-2 years) are indicative of body fat, while growth patterns beyond infancy are less indicative of fat-free mass.

Infancy is both a critical window for hypothalamic-pituitary-adrenal (HPA) axis development, and a sensitive period for social-emotional influences. We hypothesized that the social-emotional quality of maternal-infant interactions are associated with methylation of HPA-axis gene NR3C1 later in childhood.

Using a subsample of 114 mother-infant pairs from the Avon Longitudinal Study of Parents and Children (ALSPAC), linear regression models were created to predict variance in methylation of seven selected CpG sites from NR3C1 in whole blood at age 7 years, including the main predictor variable of the first principal component score of observed maternal-infant interaction quality (derived from the Thorpe Interaction Measure at 12 months of age) and covariates of cell-type proportion, maternal financial difficulties and marital status at 8 months postnatal, child birthweight, and sex.

CpG site cg27122725 methylation was negatively associated with warmer, more positive maternal interaction with her infant (β = 0.19, p = .02, q = 0.13). In sensitivity analyses, the second highest quartile of maternal behavior (neutral, hesitant behavior) was positively associated with cg12466613 methylation. The other five CpG sites were not significantly associated with maternal-infant interaction quality.

Narrow individual variation of maternal interaction with her infant is associated with childhood methylation of two CpG sites on NR3C1 that may be particularly sensitive to environmental influences. Infancy may be a sensitive period for even small influences from the social-emotional environment on the epigenetic determinants of HPA-axis function.

The vast majority of research on biobehavioral influences on development has focused on mothers and infants, whereas research on paternal biobehavioral influences remains sparse. This study aims to increase understanding of paternal influences on the biobehavioral dynamics of the family unit, using a multi-system approach.

Participants consisted of 32 predominantly high-risk families recruited during pregnancy who completed monthly questionnaires and in-home visits when infants were 4, 12, and 18 months of age. In-home visits included semi-structured interaction tasks and saliva samples for cortisol and progesterone assays.

Mothers and infants, but not fathers and infants, showed adrenocortical attunement, with the strongest attunement at 18 months. Second, mothers' couple satisfaction did not significantly impact infants' cortisol levels or mother-infant cortisol attunement, but mothers' progesterone moderated the relationship between couple satisfaction and infant cortisol levels such that mothers with low couple satisfaction, but high progesterone, had infants with lower cortisol levels. Finally, mothers' and fathers' progesterone levels were attuned across the time points.

This is some of the first evidence of the establishment of the family biorhythm and suggests that fathers play an indirect role in facilitating mother-infant adrenocortical attunement.

The online version contains supplementary material available at 10.1007/s40750-023-00215-0.

Studies have shown that prenatal maternal stress alters volumes of the amygdala and hippocampus, and alters functional connectivity between the amygdala and prefrontal cortex. However, it remains unclear whether prenatal maternal stress (PNMS) affects volumes and functional connectivity of these structures at their subdivision levels.

T1-weighted MRI and resting-state functional MRI were obtained from 19-year-old young adult offspring with (n = 39, 18 male) and without (n = 65, 30 male) exposure to PNMS deriving from the 1998 ice storm. Volumes of amygdala nuclei, hippocampal subfields and prefrontal subregions were computed, and seed-to-seed functional connectivity analyses were conducted.

Compared to controls, young adult offspring exposed to disaster-related PNMS had larger volumes of bilateral whole amygdala, driven by the lateral, basal, central, medial, cortical, accessory basal nuclei, and corticoamygdaloid transition; larger volumes of bilateral whole hippocampus, driven by the CA1, HATA, molecular layer, fissure, tail, CA3, CA4, and DG; and larger volume of the prefrontal cortex, driven by the left superior frontal. Inversely, young adult offspring exposed to disaster-related PNMS had lower functional connectivity between the whole amygdala and the prefrontal cortex (driven by bilateral frontal poles, the left superior frontal and left caudal middle frontal); and lower functional connectivity between the hippocampal tail and the prefrontal cortex (driven by the left lateral orbitofrontal).

These results suggest the possibility that effects of disaster-related PNMS on structure and function of subdivisions of offspring amygdala, hippocampus and prefrontal cortex could persist into young adulthood.

It is well known that overnutrition, overweight, and obesity in children can modulate brain mechanisms of plasticity, monoaminergic systems, and mitochondrial function. The immediate effect of overnutrition during the developmental period has not been thoroughly examined in rats until the present. This study sought to evaluate the impact on adult rats of early life overfeeding and fluoxetine treatment from post-natal day 1 (PND1) to post-natal day 21 (PND21) relative to mitochondrial function, oxidative balance, and expression of specific monoaminergic genes in the hippocampus. The following were evaluated: mitochondrial function markers, oxidative stress biomarkers, dopamine-and serotonin-related genes, and BDNF mRNA levels. Overfeeding during the lactation period deregulates cellular metabolism and the monoaminergic systems in the hippocampus. Strikingly, serotonin modulation by fluoxetine treatment protected against some of the effects of early overnutrition. We conclude that overfeeding during brain development induce detrimental effects in mitochondria and in the genes that regulate homeostatic status that can be the molecular mechanisms related to neurological diseases.

Prior research on early-life exposures to famine has established in utero development as a critical period of vulnerability to malnutrition. Yet, previous research tends to focus narrowly on this stage, at the expense of a more comprehensive examination of childhood. As a result, the literature has yet to compare the severity of the consequences of exposure to malnutrition across developmentally salient periods. Such comparison is crucial not only in the magnitude of effects but also in the nature of outcomes. Using a restricted population registry-linked health survey, this study examines the Dutch Hunger Winter to provide a comprehensive examination of the long-term consequences of in utero, infant, childhood, and adolescent exposure to famine. The results show malnutrition leads to heterogeneous effects depending on when the exposure occurs. In utero exposure to malnutrition leads to deleterious conditions in physical health and lower socioeconomic attainment. For older cohorts, results suggest a resilience to the effects of malnutrition on physical health in late life, but a higher vulnerability to socioeconomic stunting. Furthermore, the results suggest important gender differences in the long-term impact of malnutrition. Males consistently show stronger negative consequences across a wider array of conditions.

It is often assumed that the transfer of maternal glucocorticoids (GCs; e.g., corticosterone or cortisol) to offspring is an inevitable cost associated with adverse or stressful conditions experienced by mothers. However, recent evidence indicates that maternal GCs may adaptively programme particular physiological and molecular pathways during development to enhance offspring fitness. In this context, an important mechanism through which maternal GCs may lastingly affect offspring phenotypic quality and survival is via effects on embryo telomerase activity and so on offspring postnatal telomere length. Here, using a field experimental design for which we manipulated the corticosterone content in yellow-legged gull (Larus michahellis) eggs, we show that embryos from corticosterone-injected eggs not only had a higher telomerase activity but also longer telomeres just after hatching. A complementary analysis further revealed that gull hatchlings with longer telomeres had a higher survival probability during the period when most of the chick mortality occurs. Given the important role that telomere length and its restoring mechanisms have on ageing trajectories and disease risk, our findings provide a new mechanistic link by which mothers may presumably shape offspring life-history trajectories and phenotype.

Children of women with pre-eclampsia have increased risk of cardiovascular (CV) and metabolic disease in adult life. Furthermore, the risk of pregnancy complications is higher in daughters born to women affected by pre-eclampsia than in daughters born after uncomplicated pregnancies. While aberrant inflammation contributes to the pathophysiology of pregnancy complications, including pre-eclampsia, the contribution of maternal inflammation to subsequent risk of CV and metabolic disease as well as pregnancy complications in the offspring remains unclear. Here, we demonstrate that 24-week-old female rats (F1) born to dams (F0) exposed to lipopolysaccharide (LPS) during pregnancy (to induce inflammation) exhibited mild systolic dysfunction, increased cardiac growth-related gene expression, altered glucose tolerance, and coagulopathy; whereas male F1 offspring exhibited altered glucose tolerance and increased visceral fat accumulation compared with F1 sex-matched offspring born to saline-treated dams. Both male and female F1 offspring born to LPS-treated dams had evidence of anemia. Fetuses (F2) from F1 females born to LPS-treated dams were growth restricted, and this reduction in fetal growth was associated with increased CD68 positivity (indicative of macrophage presence) and decreased expression of glucose transporter-1 in their utero-placental units. These results indicate that abnormal maternal inflammation can contribute to increased risk of CV and metabolic disease in the offspring, and that the effects of inflammation may cross generations. Our findings provide evidence in support of early screening for CV and metabolic disease, as well as pregnancy complications in offspring affected by pre-eclampsia or other pregnancy complications associated with aberrant inflammation.

The use of minimally invasive biomarkers (MIBs - physiological biomarkers obtained from minimally invasive sample types) has expanded rapidly in science and medicine over the past several decades. The MIB approach is a methodological strength in the field of human and non-human primate evolutionary biology (HEB). Among humans and our closest relatives, MIBs provide unique opportunities to document phenotypic variation and to operationalize evolutionary hypotheses.

This paper overviews the use of MIBs in HEB. Our objectives are to (1) highlight key research topics which successfully implement MIBs, (2) identify promising yet under-investigated areas of MIB application, and (3) discuss current challenges in MIB research, with suggestions for advancing the field.

A range of MIBs are used to investigate focal topics in HEB, including energetics and life history variation/evolution, developmental plasticity, and social status and dominance relationships. Nonetheless, we identify gaps in existing MIB research on traits such as physical growth and gut function that are central to the field. Several challenges remain for HEB research using MIBs, including the need for additional biomarkers and methods of assessment, robust validations, and approaches that are standardized across labs and research groups. Importantly, researchers must provide better support for adaptation and fitness effects in hypothesis testing (e.g., by obtaining complementary measures of energy expenditure, demonstrating redundancy of function, and performing lifetime/longitudinal analyses). We point to continued progress in the use of MIBs in HEB to better understand the past, present, and future of humans and our closest primate relatives.

Several studies have demonstrated that a maternal low-protein diet induces long-term metabolic disorders, but the involved mechanisms are unclear. This study investigated the molecular effects of a low-protein diet during pregnancy and lactation on glucose and protein metabolism in soleus muscle isolated from adult male rats. Female rats were fed either a normal protein diet or low-protein diet during gestation and lactation. After weaning, all pups were fed a normal protein diet until the 210th day postpartum. In the 7th month of life, mass, contractile function, protein and glucose metabolism, and the Akt-mTOR pathway were measured in the soleus muscles of male pups. Dry weight and contractile function of soleus muscle in the low-protein diet group rats were found to be lower compared to the control group. Lipid synthesis was evaluated by measuring palmitate incorporation in white adipose tissue. Palmitate incorporation was higher in the white adipose tissue of the low-protein diet group. When incubated soleus muscles were stimulated with insulin, protein synthesis, total amino acid incorporation and free amino acid content, glucose incorporation and uptake, and glycogen synthesis were found to be reduced in low-protein diet group rats. Fasting glycemia was higher in the low-protein diet group. These metabolic changes were associated with a decrease in Akt and GSK-3β signaling responses to insulin and a reduction in RPS6 in the absence of the hormone. There was also notably lower expression of Akt in the isolated soleus muscle of low-protein diet group rats. This study is the first to demonstrate how maternal diet restriction can reduce skeletal muscle protein and mass by downregulating the Akt-mTOR pathway in adulthood.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) - 2019 (COVID-19) has led to a worldwide public health concern. In addition to immediate impacts on human health and well-being, COVID-19 can result in unfortunate and long-term health consequences for future generations. In particular, pregnant women and developing fetuses in low-income settings could be prone to a higher risk of undernutrition, often due to an inadequate supply of food and nutrition during a pandemic outbreak like COVID-19. Such situations can subsequently lead to an increased risk of undesirable health consequences, such as non-communicable diseases, including obesity, metabolic syndrome, hypertension, and type 2 diabetes, in individuals born to exposed mothers via fetal programming. Moreover, COVID-19 infection or related stress during pregnancy can induce long-term programming outcomes on neuroendocrinological systems in offspring after birth. However, the long-lasting consequences of the transplacental transmission of COVID-19 in offspring are currently unknown. Here we hypothesize that a COVID-19 pandemic triggers intrauterine programming outcomes in offspring due to multiple maternal factors (e.g., nutrition deficiency, stress, infection, inflammation) during pregnancy. Thus, it is crucial to establish an integrated lifetime health information system for individuals born in or around the COVID-19 pandemic to identify those at risk of adverse pre-and postnatal nutritional programming. This approach will assist in designing specific dietary or other nutritional interventions to minimize the potential undesirable outcomes in those nutritionally programmed individuals.

Maternal exposure to a high-fat diet (HFD) during pregnancy and lactation has been related to changes in the hypothalamic circuits involved in the regulation of food intake. Furthermore, maternal HFD during the critical period of development can alter the offspring's metabolic programming with long-term repercussions. This study systematically reviewed the effects of HFD consumption during pre-pregnancy, pregnancy and/or lactation. The main outcomes evaluated were food intake; body weight; cellular or molecular aspects of peptides and hypothalamic receptors involved in the regulation of energy balance in mice. Two independent authors performed a search in the electronic databases Medline/PubMed, LILACS, Web of Science, EMBASE, SCOPUS and Sigle via Open Gray. Included were experimental studies of mice exposed to HFD during pregnancy and/or lactation that evaluated body composition, food intake, energy expenditure and hypothalamic components related to energy balance. Internal validity was assessed using the SYRCLE risk of bias. The Kappa index was measured to analyze the agreement between reviewers. The PRISMA statement was used to report this systematic review. Most studies demonstrated that there was a higher body weight, body fat deposits and food intake, as well as alterations in the expression of hypothalamic neuropeptides in offspring that consumed HFD. Therefore, the maternal diet can affect the phenotype and metabolism of the offspring, in addition to harming the hypothalamic circuits and favoring the orexigenic pathways.