Prenatal Exposure to Bisphenol A at Environmentally Relevant Doses Adversely Affects the Murine Female Reproductive Tract Later in Life
Open accessAbstract
Background: Exposure to endocrine-disrupting chemicals during critical developmental periods causes adverse consequences later in life; an example is prenatal exposure to the pharmaceutical diethylstilbestrol (DES). Bisphenol A (BPA), an environmental estrogen used in the synthesis of plastics, is of concern because its chemical structure resembles that of DES, and it is a “high-volume production” chemical with widespread human exposure. Objectives: In this study we investigated whether prenatal BPA causes long-term adverse effects in female reproductive tissues in an experimental animal model previously shown useful in studying effects of prenatal DES. Methods: Timed pregnant CD-1 mice were treated on days 9–16 of gestation with BPA (0.1, 1, 10, 100, or 1,000 μg/kg/day). After delivery, pups were held for 18 months; reproductive tissues were then evaluated. Results: Ovarian cysts were significantly increased in the 1-μg/kg BPA group; ovarian cyst-adenomas were seen in the other three BPA-treated groups but not in corn-oil controls. We observed increased progressive proliferative lesions of the oviduct after BPA treatment, similar to those described in response to DES. Further, although not statistically different from the controls, prominent mesonephric (Wolffian) remnants and squamous metaplasia of the uterus, as well as vaginal adenosis, were present in BPA-treated mice, similar to lesions reported following DES treatment. More severe pathologies observed in some BPA-treated animals included atypical hyperplasia and stromal polyps of the uterus; sarcoma of the uterine cervix; and mammary adenocarcinoma. We did not observe these lesions in controls. Conclusions: These data suggest that BPA causes long-term adverse reproductive and carcinogenic effects if exposure occurs during critical periods of differentiation.
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BPA is thought to be an endocrine disruptor that acts as an estrogen mimetic.
“BPA is thought to be an endocrine disruptor that acts as an estrogen mimetic [ 128–131 ], thus research has focused largely on its effects in reproductive tissues.”
From DNA methylation: a mechanism linking environmental chemical exposures to risk of autism spectrum disorders? (2016) · cites this paper as [129]
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- Authors
- Newbold, R. R., Jefferson, W. N., & Padilla-Banks, E.
- Affiliations
- National Institutes of Health (US)
- Developmental Endocrinology and Endocrine Disruptor Section, Laboratory of Molecular Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA
- Corresponding author
- Newbold, Retha R.
- ORCID
- Jefferson, Wendy N.
- Venue
- Environmental Health Perspectives
- Publisher
- American Chemical Society (ACS)
- Published
- 2009-01-15
- Volume
- 117
- Issue
- 6
- Pages
- 879-885
- ISSN
- 0091-6765 (ISSN-L)
- 1552-9924
- PMC
- PMC2702400
- OpenAlex
- W2080879610
- Cited by
- 236
- References
- 79
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 8 · 2023: 11 · 2022: 12 · 2021: 17 · 2020: 12 · 2019: 14 · 2018: 15 · 2017: 17 · 2016: 19 · 2015: 19 · 2014: 16 · 2013: 13 · 2012: 13
- FWCI
- 12.31
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- public-domain
- creativecommons.org/licenses/by/4.0/ (vor, 3270 d)
- Locations
- Environmental Health Perspectives (publishedVersion, public-domain)
- PubMed Central (publishedVersion, public-domain)
- PubMed (publishedVersion)
- Funders
- Wake Forest University
- National Institutes of Health
- National Institute of Environmental Health Sciences
- Topics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
- Keywords
- bisphenol A, prenatal exposure, endocrine disruptors, female reproductive tract, ovarian cysts, vaginal adenosis, mammary adenocarcinoma, developmental toxicity, diethylstilbestrol
- MeSH terms
- Bisphenol A Compounds, Animals, Benzhydryl Compounds, Diethylstilbestrol, Female, Ovary, Phenols, Pregnancy, Prenatal Exposure Delayed Effects, Reproduction, Uterus, Water Pollutants, Chemical, Mice, Endocrine Disruptors
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