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Gestational Exposure to Bisphenol A Produces Transgenerational Changes in Behaviors and Gene Expression
Open accessAbstract
Bisphenol A (BPA) is a plasticizer and an endocrine-disrupting chemical. It is present in a variety of products used daily including food containers, paper, and dental sealants and is now widely detected in human urine and blood. Exposure to BPA during development may affect brain organization and behavior, perhaps as a consequence of its actions as a steroid hormone agonist/antagonist and/or an epigenetic modifier. Here we show that BPA produces transgenerational alterations in genes and behavior. Female mice received phytoestrogen-free chow with or without BPA before mating and throughout gestation. Plasma levels of BPA in supplemented dams were in a range similar to those measured in humans. Juveniles in the first generation exposed to BPA in utero displayed fewer social interactions as compared with control mice, whereas in later generations (F2 and F4), the effect of BPA was to increase these social interactions. Brains from embryos (embryonic d 18.5) exposed to BPA had lower gene transcript levels for several estrogen receptors, oxytocin, and vasopressin as compared with controls; decreased vasopressin mRNA persisted into the F4 generation, at which time oxytocin was also reduced but only in males. Thus, exposure to a low dose of BPA, only during gestation, has immediate and long-lasting, transgenerational effects on mRNA in brain and social behaviors. Heritable effects of an endocrine-disrupting chemical have implications for complex neurological diseases and highlight the importance of considering gene-environment interactions in the etiology of complex disease.
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“Altered AVP and OT neuron numbers and innervation of sexually dimorphic regions associated with social and aggressive behaviors in multiple species; anxiogenic in multiple species”
From Endocrine Disruption of Vasopressin Systems and Related Behaviors (2017) · cites this paper as [65]
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“AVP levels were also decreased in the F4 embryos of both sexes albeit to a lesser degree (64, 65).”
From Endocrine Disruption of Vasopressin Systems and Related Behaviors (2017) · cites this paper as [65]
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“Mice reared on a diet delivering approximately 170 µg/kg bw BPA (to the dams) during gestation displayed social deficits, particularly in females, that coincided with a decrease in AVP mRNA expression levels in whole embryonic brains obtained from their ED18.5 siblings (both sexes).”
From Endocrine Disruption of Vasopressin Systems and Related Behaviors (2017) · cites this paper as [65]
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“Reduced OT mRNA expression was observed in the F4 males.”
From Endocrine Disruption of Vasopressin Systems and Related Behaviors (2017) · cites this paper as [65]
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“Reduced expression of estrogen receptor, oxytocin, and vasopressin in the brain were observed and postulated to underlie the deficits in behavior of mice in the BPA lineages [ 148 ].”
From DNA methylation: a mechanism linking environmental chemical exposures to risk of autism spectrum disorders? (2016) · cites this paper as [148]
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Metadata
- Authors
- Wolstenholme, J. T., Edwards, M., Shetty, S. R. J., Gatewood, J. D., Taylor, J. A., Rissman, E. F., & Connelly, J. J.
- Affiliations
- Departments of Biochemistry and Molecular Genetics (J.T.W., M.E., S.R.J.S., J.D.G., E.F.R.)
- University of Missouri (US)
- University of Virginia (US)
- Corresponding author
- Rissman, Emilie F.
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2012-06-15
- Volume
- 153
- Issue
- 8
- Pages
- 3828-3838
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- PMC
- PMC3404345
- OpenAlex
- W2124958203
- Cited by
- 319
- References
- 79
- Citations by year
- 2026: 4 · 2025: 12 · 2024: 13 · 2023: 16 · 2022: 15 · 2021: 22 · 2020: 24 · 2019: 24 · 2018: 29 · 2017: 31 · 2016: 29 · 2015: 29 · 2014: 38 · 2013: 25 · 2012: 8
- FWCI
- 22.14
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Endocrinology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Autism Speaks (AS4802)
- National Institutes of Health
- National Institute of Mental Health (R01MH086711)
- National Institute of Environmental Health Sciences (F32ES019404)
- Topics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Sexual Differentiation and Disorders
- Keywords
- bisphenol A, endocrine disruptors, transgenerational effects, prenatal exposure, social behavior, estrogen receptor, oxytocin, vasopressin, brain gene expression, epigenetic modifications, gene-environment interaction, developmental neurotoxicity
- MeSH terms
- Bisphenol A Compounds, Animals, Benzhydryl Compounds, Female, Male, Mice, Inbred C57BL, Phenols, Pregnancy, Prenatal Exposure Delayed Effects, Social Behavior, Gene Expression, Oligonucleotide Array Sequence Analysis, Mice, Endocrine Disruptors, Real-Time Polymerase Chain Reaction
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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