title: Environmental factors, epigenetics, and developmental origin of reproductive disorders.
abstract: Sex-specific differentiation, development, and function of the reproductive system are largely dependent on steroid hormones. For this reason, developmental exposure to estrogenic and anti-androgenic endocrine disrupting chemicals (EDCs) is associated with reproductive dysfunction in adulthood. Human data in support of "Developmental Origins of Health and Disease" (DOHaD) comes from multigenerational studies on offspring of diethylstilbestrol-exposed mothers/grandmothers. Animal data indicate that ovarian reserve, female cycling, adult uterine abnormalities, sperm quality, prostate disease, and mating behavior are susceptible to DOHaD effects induced by EDCs such as bisphenol A, genistein, diethylstilbestrol, p,p'-dichlorodiphenyl-dichloroethylene, phthalates, and polyaromatic hydrocarbons. Mechanisms underlying these EDC effects include direct mimicry of sex steroids or morphogens and interference with epigenomic sculpting during cell and tissue differentiation. Exposure to EDCs is associated with abnormal DNA methylation and other epigenetic modifications, as well as altered expression of genes important for development and function of reproductive tissues. Here we review the literature exploring the connections between developmental exposure to EDCs and adult reproductive dysfunction, and the mechanisms underlying these effects.
authors.affiliation: Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, OH, United States; Center for Environmental Genetics, University of Cincinnati College of Medicine, Cincinnati, OH, United States; Cincinnati Cancer Center, Cincinnati, OH, United States; Cincinnati Veteran Affairs Hospital Medical Center, Cincinnati, OH, United States. Electronic address: shuk-mei.ho@uc.edu.
authors.forename: Shuk-Mei
authors.initials: SM
authors.lastname: Ho
authors.affiliation: Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, OH, United States; Center for Environmental Genetics, University of Cincinnati College of Medicine, Cincinnati, OH, United States.
authors.forename: Ana
authors.initials: A
authors.lastname: Cheong
authors.affiliation: Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, United States.
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Adgent
authors.affiliation: Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, OH, United States; Cincinnati Cancer Center, Cincinnati, OH, United States.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Veevers
authors.affiliation: Reproductive Medicine Group, Reproductive & Developmental Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC, United States; Curriculum in Toxicology, UNC Chapel Hill, Chapel Hill, NC, United States.
authors.forename: Alisa A
authors.initials: AA
authors.lastname: Suen
authors.affiliation: Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, OH, United States; Center for Environmental Genetics, University of Cincinnati College of Medicine, Cincinnati, OH, United States; Cincinnati Cancer Center, Cincinnati, OH, United States.
authors.forename: Neville N C
authors.initials: NNC
authors.lastname: Tam
authors.affiliation: Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, OH, United States; Center for Environmental Genetics, University of Cincinnati College of Medicine, Cincinnati, OH, United States; Cincinnati Cancer Center, Cincinnati, OH, United States.
authors.forename: Yuet-Kin
authors.initials: YK
authors.lastname: Leung
authors.affiliation: Reproductive Medicine Group, Reproductive & Developmental Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC, United States.
authors.forename: Wendy N
authors.initials: WN
authors.lastname: Jefferson
authors.affiliation: Reproductive Medicine Group, Reproductive & Developmental Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC, United States. Electronic address: williamsc5@niehs.nih.gov.
authors.forename: Carmen J
authors.initials: CJ
authors.lastname: Williams
mesh_terms: D000818:Animals; D052244:Endocrine Disruptors / Q000633:toxicity*; D004781:Environmental Exposure / Q000009:adverse effects*; D044127:Epigenesis, Genetic / Q000187:drug effects*; D005260:Female; D005865:Gestational Age; D006801:Humans; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000235:genetics; D012098:Reproduction / Q000187:drug effects* / Q000235:genetics
chemical_list: D052244:Endocrine Disruptors
keywords: DNA methylation; Developmental programming; Epigenetic reprogramming; Histone modification; Non-coding RNA; Reproductive behaviors; Reproductive dysfunction; Transgenerational transmission