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Reprod Toxicol. 2017 Mar;68:85-104. doi: 10.1016/j.reprotox.2016.07.011. Epub 2016 Jul 12.

Environmental factors, epigenetics, and developmental origin of reproductive disorders.

Author information

1
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.
2
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.
3
Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, United States.
4
Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, OH, United States; Cincinnati Cancer Center, Cincinnati, OH, United States.
5
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.
6
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.
7
Reproductive Medicine Group, Reproductive & Developmental Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC, United States.
8
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.

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.

KEYWORDS:

DNA methylation; Developmental programming; Epigenetic reprogramming; Histone modification; Non-coding RNA; Reproductive behaviors; Reproductive dysfunction; Transgenerational transmission

PMID:
27421580
PMCID:
PMC5233640
DOI:
10.1016/j.reprotox.2016.07.011
[Indexed for MEDLINE]
Free PMC Article

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