• China
• cryptorchidism
• epidemiology
• prevalence

• Humans
• Cryptorchidism/epidemiology
• China/epidemiology
• Male
• Prevalence
• Infant, Newborn
• Adult
• Female
• Population Surveillance
• Young Adult
• Maternal Age

• National Health Commission of China

• animal models
• environmental chemicals
• epigenetics
• metabolic health
• reproduction
• transgenerational

• Animals
• Humans
• Female
• Environmental Pollutants/toxicity
• Environmental Pollutants/adverse effects
• Environmental Exposure/adverse effects
• Reproduction/drug effects
• Male
• Pregnancy
• Mammals

• cryptorchidism
• endocrine disrupting compounds
• epidemiology
• prenatal exposure
• testicular dysgenesis

• Pregnancy
• Female
• Humans
• Male
• Infant, Newborn
• Cryptorchidism/epidemiology
• Testicular Neoplasms/complications
• Endocrine Disruptors
• Prospective Studies
• Semen Analysis
• Premature Birth
• Risk Factors

• Hypospadias
• Pediatrics
• TIP
• Urethral advancement

• Diet
• Fertility
• Reproductive health
• Semen
• Sperm
• Testosterone

• France
• birth defects
• cryptorchidism
• disease spatial clusters
• endocrine disruptors
• environment
• epidemiology
• incidence rate
• reproductive health

The incidence of breast cancer among women of reproductive age is increasing, as well as the desire for children at late childbearing age. Identifying factors that may be associated with fetal malformation and maternal and fetal prognosis has gained importance. We describe a 32-year-old woman with breast cancer who gave birth to a son with congenital bilateral cryptorchidism after treatment, with a literature review performed.

A 32-year-old woman with breast cancer who had been treated by surgery and radiotherapy experienced recurrence and underwent a second surgery, adjuvant chemotherapy, and targeted therapy. Her tumor cells were negative for estrogen receptor (ER) α, progesterone receptor (PR), and p53; positive for ERβ, human epidermal growth factor receptor-2 (HER2), epidermal growth factor receptor (EGFR), and Ki67. She had pathogenic BRCA gene mutations. She became pregnant within 2 years and delivered a boy with congenital bilateral cryptorchidism. The boy underwent bilateral orchidopexy. As of this writing, the woman and her son are both healthy.

HER2 overexpression, positivity for EGFR, Ki67, and ER, and PR negativity are associated with a poor prognosis in breast cancer. While no link has been established statistically between treatment for breast cancer and cryptorchidism in a subsequent pregnancy, this case suggests the possibility that ERβ and gene mutations may be contributing factors.

• Pregnancy
• Breast cancer
• Chemotherapy
• Cryptorchidism
• Case report

Urogenital tract abnormalities are among the most common congenital defects in humans. Male urogenital development requires Hedgehog-GLI signaling and testicular hormones, but how these pathways interact is unclear. We found that Gli3^XtJ mutant mice exhibit cryptorchidism and hypospadias due to local effects of GLI3 loss and systemic effects of testicular hormone deficiency. Fetal Leydig cells, the sole source of these hormones in developing testis, were reduced in numbers in Gli3^XtJ testes, and their functional identity diminished over time. Androgen supplementation partially rescued testicular descent but not hypospadias in Gli3^XtJ mutants, decoupling local effects of GLI3 loss from systemic effects of androgen insufficiency. Reintroduction of GLI3 activator (GLI3A) into Gli3^XtJ testes restored expression of Hedgehog pathway and steroidogenic genes. Together, our results show a novel function for the activated form of GLI3 that translates Hedgehog signals to reinforce fetal Leydig cell identity and stimulate timely INSL3 and testosterone synthesis in the developing testis. In turn, exquisite timing and concentrations of testosterone are required to work alongside local GLI3 activity to control development of a functionally integrated male urogenital tract.

Disorders in male sex differentiation (DSD) are among the most common defects in all live births, yet in many cases, pediatric patient families are reluctant to address the issue and endure lifelong consequences. Urogenital tract development, as in many organ systems, depends on exquisite timing among layers of a number of signaling pathways. Here, we show that interactions between the hedgehog and androgen signaling pathways are required for the development of internal and external male sex characteristics, but results for each tissue is distinct. This new knowledge will aid in discovering the means by which congenital malformations might occur, identify potential developmental targets that might be vulnerable to environmental exposures, and promote new ideas for how they might be prevented.

• congenital malformation
• genitalia
• hypospadias
• penis development
• pollutant
• teratogen

• Adolescent
• Adult
• Air Pollutants/analysis
• Air Pollution, Indoor/adverse effects
• Female
• Hazardous Substances/adverse effects
• Humans
• Hypospadias/chemically induced
• Hypospadias/epidemiology
• Male
• Maternal Exposure/adverse effects
• Metals, Heavy/adverse effects
• Pregnancy
• Prenatal Exposure Delayed Effects/chemically induced
• Prenatal Exposure Delayed Effects/epidemiology
• Risk Factors
• Texas/epidemiology
• Young Adult

• R01 DK078121 NIDDK NIH HHS
• T32 DK007763 NIDDK NIH HHS
• K12 DK083014 NIDDK NIH HHS

Little information is available on the prevalences of birth defects in Korea. The aims of this study were to estimate recent prevalences of selected birth defects and to analyze the prevalence trends of these defects during the period from 2008 to 2014. Prevalences were calculated for 69 major birth defects using health insurance claim data obtained from the Korea National Health Insurance Service (NHIS). Prevalence rate ratios were calculated using Poisson regression to analyze trends over the 7-year study period. The overall prevalence of a major birth defect was 446.3 per 10,000 births (95% CI: 444.0–448.6); 470.9 per 10,000 births (95% CI: 467.6–474.2) for males and 420.2 per 10,000 births (95% CI: 417–423.4) for females. The prevalence rates of the most common birth defects over the study period were; septal defect (138.2 per 10,000; 95% CI: 136.9–139.5), congenital hip dislocation (652 per 10,000; 95% CI: 64.1–65.9), and ventricular septal defect (62.62 per 10,000; 95% CI: 61.7–63.5). During the study period, a significant increase in the prevalence of a major birth defect was observed with a prevalence rate ratio (PRR) of 1.091. The strongest trend was observed for renal dysplasia, which had a PRR of 1.275 (95% CI: 1.211–1.343), and upward trends were observed for urogenital anomalies, such as, renal agenesis (PRR 1.102, 95% CI: 1.067–1.138), undescended testis (PRR 1.082, 95% CI: 1.072–1.093) and hypospadias (PRR 1.067, 95% CI: 1.044–1.090). This study shows an overall increase in the prevalences of birth defects, including hypospadias and undescended testis, which are known to be associated with endocrine factors. In the future, standardized birth defect registries should be established to enable these trends to be monitored.

• birth defects
• congenital heart defects
• prevalence rate ratios
• trends
• urogenital anomalies

• Cluster analysis
• Cryptorchidism
• Epidemiology
• Hypospadias
• Prevalence

• Epidemiology
• Hypospadias
• Incidence
• Prevalence

Birth defects are a leading cause of neonatal and infant mortality, and several studies have indicated an increase in the prevalence of birth defects; more recent investigations have suggested that the trends of some defects are increasing in rapidly industrialized areas. This study estimates the prevalence rate and types of birth defects in Korea.

This study used medical insurance benefit data of 403,250 infants aged less than one year from the National Health Insurance Corporation from seven metropolitan areas in Korea for 2009 and 2010.

The prevalence rate of birth defects was 548.3 per 10,000 births (95 % CI: 541.1–555.6), 306.8 among boys and 241.5 among girls. Anomalies of the circulatory system (particularly septal defects) were the most common (180.8 per 10,000), followed by defects of the genitourinary tract (130.1 per 10,000) (particularly obstructive genitourinary and undescended testis), musculoskeletal system (105.7 per 10,000), digestive system (24.7 per 10,000), and central nervous system (15.6 per 10,000).

Relatively higher rates of some birth defects were found in the metropolitan areas. The high differences of birth prevalences for septal heart defects and undescended testis are probably due in part to progress in clinical management and more frequent prenatal diagnosis. Environmental exposure might play a critical role in the development of some birth defects. In attempting to describe the prevalence and spatio-temporal variations of birth defects in Korea, establishment of a registry system of birth defects and environmental surveillance are needed.

• Birth defects
• Korea
• Prevalence

This case-controlled study was designed to evaluate the association between various baseline parental factors and the risk of hypospadias in China. Patients were selected from tertiary referral hospitals in Anhui, a province in mid-eastern China. A questionnaire was given to the parents of each patient. The final database included 193 cases and 835 controls. The incidence of additional coexistent anomalies was 13.0%, primarily cryptorchidism (9.8%). Ten patients (5.1%) were from families with genital anomaly, including five families (2.6%) with hypospadias. The risks of hypospadias was higher for children of mothers > 35 (odds ratio [OR] =1.47) and < 18 (OR = 2.95) years of age, and in mothers who had consumed alcohol (OR = 2.67), used drugs (OR = 1.53) and had an infection (OR = 1.87) during pregnancy. The risk of hypospadias was also higher when mothers (OR = 1.68) and fathers (OR = 1.74) were engaged in agriculture. Other factors assessed were not associated with the risk of hypospadias.

• Animals
• Disorders of Sex Development/complications
• Endocrine Disruptors/adverse effects
• Female
• Fetal Growth Retardation/physiopathology
• Humans
• Infertility, Male/etiology
• Klinefelter Syndrome/genetics
• Klinefelter Syndrome/physiopathology
• Male
• Mothers
• Pregnancy
• Prenatal Exposure Delayed Effects
• Smoking/adverse effects
• Testicular Neoplasms/embryology
• Testis/abnormalities
• Testis/embryology
• Testosterone/blood

• Diet/adverse effects
• Female
• Humans
• Hypospadias/etiology
• Life Style
• Male
• Maternal Exposure/adverse effects
• Pregnancy
• Urologic Surgical Procedures, Male/methods