Perinatal exposure to bisphenol-A changes N-methyl-D-aspartate receptor expression in the hippocampus of male rat offspring
Open accessAbstract
Bisphenol-A (BPA) is one of the most common environmental endocrine disrupters with mixed estrogen agonist/antagonist properties. The toxicity of BPA has been extensively evaluated in a variety of tests in rodents, including developmental and reproductive toxicity, and carcinogenicity. The objective of the present study is to evaluate whether or not perinatal maternal exposure to BPA at 0.05, 0.5, 5, 50, and 200 mg/kg/d affects N-methyl-D-aspartate (NMDA) receptor (NMDAR) subunits NR1, NR2A, 2B, estrogen receptor beta (ERβ), and aromatase cytochrome P450 (P450arom) protein expressions of hippocampus in male rat offspring during postnatal development. Western-blotting analyses showed that perinatal exposure to BPA significantly affected the expression of NMDAR subunits. At the lower doses of 0.05 to 50 mg/kg/d, BPA concentration dependently inhibited the expression of NMDAR subunits. However, at the higher dose (200 mg/kg/d), the effects of BPA on these subunits were different, with a stronger inhibition of NR1 expression and a slighter inhibition of NR2A, 2B expression when compared with those at the lower dosage of BPA. In addition, perinatal exposure to BPA inhibited the expression of ERβ protein, but increased P450arom protein expression in a concentration-dependent manner, especially during the early postnatal period (the first 1–3 postnatal weeks). No significant influence of BPA on P450arom was observed at postnatal week 8. These data suggest that environmental BPA exposure may affect the development of the brain, enhancing the local biosynthesis of estrogen in the brain, inhibiting ERβ and NMDAR expressions. Environ. Toxicol. Chem. 2010;29:176–181. © 2009 SETAC
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In male mice exposed to low doses of BPA probably comparable to ours, mRNA for ERβ and several NMDA receptors were decreased in hippocampus at days 21 and 56.
“In male mice, exposed to low doses of BPA that are probably comparable to ours, mRNA for ERβ and several of the NMDA receptors were decreased in hippocampus at day 21 and 56 [33].”
From Gestational Exposure to Low Dose Bisphenol A Alters Social Behavior in Juvenile Mice (2011) · cites this paper as [33]
The Abstract and Results ('Expressions of NR subunits' and 'Expressions of ERb and P450arom'; page numbers unavailable) report reduced hippocampal NMDA-receptor subunit and ERβ expression after perinatal BPA exposure. But the offspring were male rats, not mice, and Western blots measured protein, not mRNA. The Results also report significant ERβ reduction at all postnatal time points for the highest dose, not for low doses at both days 21 and 56. (LLM, conf=0.93)
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Estradiol and the Developing Brain
McCARTHY, M. M. (2008) · Physiological Reviews · doi:10.1152/physrev.00010.2007 · Cited by 885 · see citing works
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Research works printed but not linked: 2
- X.-H. Xu et al. 15528618, 2010, 1, Downloaded from https://setac.onlinelibrary.wiley.com/doi/10.1002/etc.18 by Test, Wiley Online Library on [31/08/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License In vivo effects of bisphenol A in laboratory rodent studies. Reprod Toxicol 24:199-224. · DOI
- Lephart ED. 1996. A review of brain aromatase cytochrome P450. Brain Res Rev 22:1-26.
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Prenatal Bisphenol A Exposure and Child Behavior in an Inner-City Cohort
Perera, F., Vishnevetsky, J., Herbstman, J. B., Calafat, A. M., Xiong, W., Rauh, V., & Wang, S. (2012) · Environmental Health Perspectives · doi:10.1289/ehp.1104492 · Cited by 332 · see citing works
Gestational Exposure to Low Dose Bisphenol A Alters Social Behavior in Juvenile Mice
Wolstenholme, J. T., Taylor, J. A., Shetty, S. R. J., Edwards, M., Connelly, J. J., & Rissman, E. F. (2011) · PLoS ONE · doi:10.1371/journal.pone.0025448 · Cited by 168 · see citing works
“In male mice, exposed to low doses of BPA that are probably comparable to ours, mRNA for ERb and several of the NMDA receptors were decreased in hippocampus at day 21 and 56 [33].”
BackgroundMethodKumar, D., & Thakur, M. K. (2014) · PLoS ONE · doi:10.1371/journal.pone.0110482 · Cited by 37 · see citing works
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- Authors
- Xu, X.-H., Wang, Y.-M., Zhang, J., Luo, Q.-Q., Ye, Y.-P., & Ruan, Q.
- Affiliations
- Zhejiang Normal University (CN)
- Chemistry and Life Science College, Zhejiang Normal University, Jinhua 321004, People's Republic of China
- Corresponding author
- Xu, Xiao-Hong
- ORCID
- Zhang, Jing
- Venue
- Environmental Toxicology and Chemistry
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-01-01
- Volume
- 29
- Issue
- 1
- Pages
- 176-181
- ISSN
- 0730-7268 (ISSN-L)
- 1552-8618
- OpenAlex
- W2056736352
- Cited by
- 53
- References
- 1
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 2 · 2022: 3 · 2021: 3 · 2020: 3 · 2019: 4 · 2018: 10 · 2017: 2 · 2016: 2 · 2015: 4 · 2014: 3 · 2013: 5 · 2012: 5
- FWCI
- 3.66
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Environmental Toxicology and Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (30771783, 30872087, Z2090955)
- 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 › Pediatrics, Perinatology and Child Health › Pharmacological Effects and Toxicity Studies
- Keywords
- bisphenol A, perinatal exposure, NMDA receptor, hippocampus, NR1, NR2A, NR2B, estrogen receptor beta, aromatase, P450arom, endocrine disruptors, postnatal brain development, dose-dependent effects
- MeSH terms
- Bisphenol A Compounds, Animals, Aromatase, Benzhydryl Compounds, Dose-Response Relationship, Drug, Female, Fetus, Hippocampus, Male, Phenols, Pregnancy, Receptors, N-Methyl-D-Aspartate, Rats, Sprague-Dawley, Estrogen Receptor beta, Rats, Endocrine Disruptors
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