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The role of Bisphenol A in shaping the brain, epigenome and behavior
Open accessAbstract
Bisphenol A (BPA) is a xenoestrogen that was first synthesized in 1891. Its estrogenic properties were discovered in 1930, and shortly after that chemists identified its usefulness in the production of epoxy resins. Since the 1950s BPA has been used as a synthetic monomer in the manufacturing of polycarbonate plastic, polystyrene resins, and dental sealants. Roughly 6.5 billion pounds of BPA are produced each year and it is the major estrogenic compound that leaches into nearby water and food supplies (vom Saal et al., 2007). BPA has been detected in 95% of human urine samples, which indicates that environmental exposure is widespread (Calafat et al., 2005). Moreover, BPA affects reproductive tissues and the brain. Thus many studies have focused on the effects of BPA during embryonic development. The most recent FDA update (Administration January 2010) points to "some concern about the potential effects of Bisphenol A on the brain, behavior, and prostate gland in fetuses, infants, and young children." In light of this concern, we present an updated review of BPA's action on the brain and behavior. We begin with a discussion of BPA's role as both an endocrine active compound and an agent that alters DNA methylation. Next, we review publications that have reported effects of BPA on brain and behavior. We end with our interpretation of these data and suggestions for future research directions.
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“Dysregulation of DNA methylation during these critical developmental windows could disrupt the normal progression of brain and endocrine system development causing robust changes in the developing embryo that can persist into adulthood or even beyond if effects extend to germ cells [30].”
From Gestational Exposure to Low Dose Bisphenol A Alters Social Behavior in Juvenile Mice (2011) · cites this paper as [30]
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“Nevertheless, linkages between developmental BPA exposure and an anxiogenic phenotype have repeatedly been shown in dozens of studies using a variety of animal models and human populations (representative examples include (62, 91, 93, 96–100)).”
From Endocrine Disruption of Vasopressin Systems and Related Behaviors (2017) · cites this paper as [93]
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Epigenetic programming by maternal behavior
Weaver, I. C. G., Cervoni, N., Champagne, F. A., D'Alessio, A. C., Sharma, S., Seckl, J. R., Dymov, S., Szyf, M., & Meaney, M. J. (2004) · Nature Neuroscience · doi:10.1038/nn1276 · Cited by 6,177
Human DNA methylomes at base resolution show widespread epigenomic differences
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Interaction of Estrogenic Chemicals and Phytoestrogens with Estrogen Receptor β
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Epigenetic Transgenerational Actions of Endocrine Disruptors and Male Fertility
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Epigenetic inheritance at the agouti locus in the mouse
Morgan, H. D., Sutherland, H. G. E., Martin, D. I. K., & Whitelaw, E. (1999) · Nature Genetics · doi:10.1038/15490 · Cited by 1,476
Dolinoy, D. C., Huang, D., & Jirtle, R. L. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0703739104 · Cited by 1,369
Active DNA demethylation: many roads lead to Rome
Wu, S. C., & Zhang, Y. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2950 · Cited by 1,091
Urinary Concentrations of Bisphenol A and 4-Nonylphenol in a Human Reference Population
Calafat, A. M., Kuklenyik, Z., Reidy, J. A., Caudill, S. P., Ekong, J., & Needham, L. L. (2005) · Environmental Health Perspectives · doi:10.1289/ehp.7534 · Cited by 1,031
Dolinoy, D. C., Weidman, J. R., Waterland, R. A., & Jirtle, R. L. (2006) · Environmental Health Perspectives · doi:10.1289/ehp.8700 · Cited by 943
Neuronal Activity–Induced Gadd45b Promotes Epigenetic DNA Demethylation and Adult Neurogenesis
Dengke, K., Jang, M., Guo, J. U., Kitabatake, Y., Chang, M.-L., Pow-anpongkul, N., Flavell, R. A., Lu, B., Ming, G., & Song, H. (2009) · Science · doi:10.1126/science.1166859 · Cited by 929
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(2013) · PubMed · Cited by 22
Metadata
- Authors
- Wolstenholme, J. T., Rissman, E. F., & Connelly, J. J.
- Affiliations
- University of Virginia (US)
- Corresponding author
- Connelly, Jessica J.
- Venue
- Hormones and Behavior
- Publisher
- Elsevier BV
- Published
- 2011-03
- Volume
- 59
- Issue
- 3
- Pages
- 296-305
- ISSN
- 0018-506X (ISSN-L)
- PMC
- PMC3725332
- OpenAlex
- W2044819518
- Cited by
- 309
- References
- 98
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 14 · 2023: 16 · 2022: 18 · 2021: 12 · 2020: 21 · 2019: 25 · 2018: 36 · 2017: 15 · 2016: 32 · 2015: 24 · 2014: 18 · 2013: 27 · 2012: 22
- FWCI
- 1.94
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Hormones and Behavior (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- 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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Keywords
- bisphenol A, xenoestrogens, endocrine disruptors, brain development, behavior, DNA methylation, epigenetics, embryonic development, prenatal exposure, polycarbonate plastics, estrogenic activity
- MeSH terms
- Bisphenol A Compounds, Animals, Behavior, Animal, Benzhydryl Compounds, Brain, Estrogens, Non-Steroidal, Female, Humans, Learning, Maternal Behavior, Phenols, Pregnancy, Prenatal Exposure Delayed Effects, Sex Characteristics, Epigenesis, Genetic
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