Investigation of the effects of subchronic low dose oral exposure to bisphenol A (BPA) and ethinyl estradiol (EE) on estrogen receptor expression in the juvenile and adult female rat hypothalamus
Open accessAbstract
Concerns have been raised regarding the long-term impacts of early life exposure to the ubiquitous environmental contaminant bisphenol A (BPA) on brain organization. Because BPA has been reported to affect estrogen signaling, and steroid hormones play a critical role in brain sexual differentiation, there is also concern that BPA exposure could alter neural sex differences. Here, we examine the impact of subchronic exposure from gestation to adulthood to oral doses of BPA below the current no-observed-adverse-effect level (NOAEL) of 5 mg/kg body weight (bw)/day on estrogen receptor (ESR) expression in sexually dimorphic brain regions of prepubertal and adult female rats. The dams were gavaged daily with vehicle (0.3% carboxymethylcellulose), 2.5, 25, 260, or 2700 μg BPA/kg bw/day, or 0.5 or 5.0 μg ethinyl estradiol (EE)/kg bw/day from gestational day 6 until labor began. Offspring were then gavaged directly from the day after birth until the day before scheduled sacrifice on postnatal days 21 or 90. Using in situ hybridization, one or more BPA doses produced significant decreases in Esr1 expression in the juvenile female rat anteroventral periventricular nucleus (AVPV) of the hypothalamus and significant decreases in Esr2 expression in the adult female rat AVPV and medial preoptic area (MPOA), relative to vehicle controls. BPA did not simply reproduce EE effects, indicating that BPA is not acting solely as an estrogen mimic. The possible consequences of long-term changes in h…
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Developmental exposure to doses as low as 2.5 μg/kg bw sex specifically alters the mRNA expression of ERα and ERβ in sexually dimorphic hypothalamic and limbic subnuclei in the neonatal and older rat brain.
“For example, we have repeatedly shown that developmental exposure to doses as low as 2.5 µg/kg bw sex specifically alters the mRNA expression of ERα and ERβ in sexually dimorphic hypothalamic and limbic subnuclei in the neonatal and older rat brain (86–90).”
From Endocrine Disruption of Vasopressin Systems and Related Behaviors (2017) · cites this paper as [87]
Developmental BPA exposure can perturb ERα and ERβ gene expression throughout the rat hypothalamus and components of the mesolimbic dopamine system, including the PVN and BnST, across the lifespan.
“We have repeatedly shown that developmental BPA exposure can perturb ERα and ERβ gene expression throughout the rat hypothalamus and components of the mesolimbic dopamine system, including the PVN and BnST (86–90), across the lifespan.”
From Endocrine Disruption of Vasopressin Systems and Related Behaviors (2017) · cites this paper as [87]
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EDC-2: the endocrine society's second scientific statement on endocrine-disrupting chemicals
Gore, A. C., Chappell, V. A., Fenton, S. E., Flaws, J. A., Nadal, A., Prins, G. S., Toppari, J., & Zoeller, R. T. (2015) · Endocrine Reviews · doi:10.1210/er.2015-1010 · Cited by 2,407 · see citing works
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Self-citationEndocrine Disruption of Vasopressin Systems and Related Behaviors
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- Authors
- Rebuli, M. E., Cao, J., Sluzas, E., Delclos, K. B., Camacho, L., Lewis, S. M., Vanlandingham, M. M., & Patisaul, H. B.
- Affiliations
- North Carolina State University (US)
- National Center for Toxicological Research (US)
- Corresponding author
- Patisaul, Heather B.
- ORCID
- Venue
- Toxicological Sciences
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-04-20
- Volume
- 140
- Issue
- 1
- Pages
- 190-203
- ISSN
- 1096-0929 (ISSN-L)
- 1096-6080
- PMC
- PMC4133590
- OpenAlex
- W2143926865
- Cited by
- 83
- References
- 9
- Citations by year
- 2025: 3 · 2024: 4 · 2023: 5 · 2022: 5 · 2021: 5 · 2020: 5 · 2019: 12 · 2018: 13 · 2017: 11 · 2016: 5 · 2015: 11 · 2014: 4
- FWCI
- 6.79
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- public-domain
- Locations
- Toxicological Sciences (publishedVersion, public-domain)
- PubMed Central (publishedVersion, public-domain)
- PubMed (publishedVersion)
- Funders
- U.S. Public Health Service (R01-16001-04S1, AES12013, 224-12-0003)
- National Institute of Environmental Health Sciences (R21ES021233)
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Keywords
- bisphenol A, ethinyl estradiol, estrogen receptor expression, estrogen receptor alpha, estrogen receptor beta, hypothalamus, anteroventral periventricular nucleus, medial preoptic area, sexual differentiation of the brain, early life exposure, female rats, neuroendocrine effects, environmental endocrine disruptors
- MeSH terms
- Bisphenol A Compounds, Aging, Animals, Benzhydryl Compounds, Dose-Response Relationship, Drug, Ethinyl Estradiol, Female, Hypothalamus, Male, Phenols, Pregnancy, Prenatal Exposure Delayed Effects, Receptors, Estrogen, Sex Characteristics, Gene Expression, Rats, Sprague-Dawley, Estrogen Receptor alpha, Estrogen Receptor beta
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