Environmental factors, epigenetics, and developmental origin of reproductive disorders
Open accessAbstract
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.
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Endometriosis can be established as a developmental condition, within the general paradigm of DoHAD.
“Probably the most important long-term implication of the recent findings that link endometriosis with low prenatal testosterone is that they begin to establish endometriosis as a developmental condition, within the general paradigm of DoHAD, the developmental origins of health and adult disease.86”
From Prenatal Origins of Endometriosis Pathology and Pain: Reviewing the Evidence of a Role for Low Testosterone (2023) · cites this paper as [86]
Section 2.1 (Female; page unavailable) reports that prenatal DES exposure was associated with increased endometriosis risk, supporting a developmental link within the paper’s DOHaD framework. It does not report the citing sentence’s specific link between endometriosis and low prenatal testosterone. (LLM, conf=0.85)
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References 223 · Cited by 226
Research works printed but not linked: 1
- [189]Shirlaw L Seek an effective treatment for addiction to alcohol Alcohol Alcohol 26 5–6 1991 651 3 1804146
- Authors
- Ho, S.-M., Cheong, A., Adgent, M. A., Veevers, J., Suen, A. A., Tam, N. N. C., Leung, Y.-K., Jefferson, W. N., & Williams, C. J.
- Affiliations
- Cincinnati VA Medical Center (US)
- University of Cincinnati (US)
- Vanderbilt University Medical Center (US)
- University of North Carolina at Chapel Hill (US)
- National Institutes of Health (US)
- Corresponding author
- Ho, Shuk-Mei
- Williams, Carmen J.
- ORCID
- Venue
- Reproductive Toxicology
- Publisher
- Elsevier BV
- Published
- 2017-03
- Volume
- 68
- Pages
- 85-104
- ISSN
- 0890-6238 (ISSN-L)
- PMC
- PMC5233640
- OpenAlex
- W2463634629
- Cited by
- 226
- References
- 223
- Citations by year
- 2026: 13 · 2025: 26 · 2024: 22 · 2023: 24 · 2022: 23 · 2021: 34 · 2020: 27 · 2019: 21 · 2018: 20 · 2017: 14 · 2016: 2
- FWCI
- 11.96
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Reproductive Toxicology (acceptedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- National Institutes of Environmental Health Sciences (ZIAES102405)
- National Cancer Institute (RC2ES018758, RC2ES018789, R01CA062269, R01ES022071, R01ES015584, R21ES013071, U01ES019480, U01ES020988, P30ES006096)
- United States Department of Veterans Affairs (I01BX000675, R21CA156042)
- Department of Defense Prostate Cancer Research Program (W81XWH-15-1-0496)
- Intramural Research Program of the National Institutes of Health
- Topics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Keywords
- endocrine disruptors, developmental origins of health and disease, reproductive disorders, epigenetics, DNA methylation, diethylstilbestrol, bisphenol A, genistein, DDT, phthalates, polycyclic aromatic hydrocarbons, steroid hormones, ovarian reserve, semen quality, uterine abnormalities, prostate diseases, mating behavior
- MeSH terms
- Animals, Environmental Exposure, Female, Gestational Age, Humans, Pregnancy, Prenatal Exposure Delayed Effects, Reproduction, Epigenesis, Genetic, Endocrine Disruptors
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