The Environmental Estrogen Bisphenol A Inhibits Estradiol-Induced Hippocampal Synaptogenesis
Open accessAbstract
Bisphenol A (BPA) is an estrogenic chemical that is widely used in the manufacture of plastics and epoxy resins. Because BPA leaches out of plastic food and drink containers, as well as the BPA-containing plastics used in dental prostheses and sealants, considerable potential exists for human exposure to this compound. In this article we show that treatment of ovariectomized rats with BPA dose-dependently inhibits the estrogen-induced formation of dendritic spine synapses on pyramidal neurons in the CA1 area of the hippocampus. Significant inhibitory effects of BPA were observed at a dose of only 40 μg/kg, below the current U.S. Environmental Protection Agency reference daily limit for human exposure. Because synaptic remodeling has been postulated to contribute to the rapid effects of estrogen on hippocampus-dependent memory, these data suggest that environmental BPA exposure may interfere with the development and expression of normal sex differences in cognitive function, via inhibition of estrogen-dependent hippocampal synapse formation. It may also exacerbate the impairment of hippocampal function observed during normal aging, as endogenous estrogen production declines.
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The E2-induced increase in synapse density is inhibited by simultaneous application of BPA (40 ug/kg) and E2 (60 ug/kg) in ovariectomized rats for 30 min.
“Our findings are consistent with a previous in vivo study showing that the E2-induced increase in synapse density is inhibited by the simultaneous application of BPA (40 ug/kg) and E2 (60 ug/kg) in ovariectomized rats for 30 min [37].”
From The Rapid Effect of Bisphenol-A on Long-Term Potentiation in Hippocampus Involves Estrogen Receptors and ERK Activation (2017) · cites this paper as [37]
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- Authors
- MacLusky, N. J., Hajszan, T., & Leranth, C.
- Affiliations
- Helen Hayes Hospital (US)
- 2Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut, USA
- Yale University (US)
- ORCID
- MacLusky, Neil J.
- Venue
- Environmental Health Perspectives
- Publisher
- American Chemical Society (ACS)
- Published
- 2005-02-24
- Volume
- 113
- Issue
- 6
- Pages
- 675-679
- ISSN
- 0091-6765 (ISSN-L)
- 1552-9924
- PMC
- PMC1257590
- OpenAlex
- W2052927712
- Cited by
- 196
- References
- 1
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 4 · 2022: 4 · 2021: 9 · 2020: 11 · 2019: 9 · 2018: 13 · 2017: 10 · 2016: 6 · 2015: 8 · 2014: 17 · 2013: 10 · 2012: 11
- FWCI
- 9.21
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- public-domain
- creativecommons.org/licenses/by/4.0/ (vor, 4691 d)
- Locations
- Environmental Health Perspectives (publishedVersion, public-domain)
- PubMed Central (publishedVersion, public-domain)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (MH60858)
- National Institute of Mental Health (R01MH060858, MH 60858)
- National Institute of Neurological Disorders and Stroke (NS 42644, R01NS042644)
- 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 › Pathology and Forensic Medicine › Phytoestrogen effects and research
- Keywords
- bisphenol A, xenoestrogens, estradiol, hippocampus, synaptogenesis, dendritic spines, CA1 pyramidal neurons, synaptic remodeling, sex differences in cognition, ovariectomy, plastic leaching, human exposure, aging, memory
- MeSH terms
- Bisphenol A Compounds, Animals, Benzhydryl Compounds, Estradiol, Estrogens, Non-Steroidal, Female, Ovariectomy, Phenols, Synapses, Rats, Sprague-Dawley, Pyramidal Cells, Dendritic Spines, Rats
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