Evidence of altered brain sexual differentiation in mice exposed perinatally to low, environmentally relevant levels of bisphenol A.
Abstract
Humans are routinely exposed to bisphenol A (BPA), an estrogenic chemical present in food and beverage containers, dental composites, and many products in the home and workplace. BPA binds both classical nuclear estrogen receptors and facilitates membrane-initiated estrogenic effects. Here we explore the ability of environmentally relevant exposure to BPA to affect anatomical and functional measures of brain development and sexual differentiation. Anatomical evidence of alterations in brain sexual differentiation were examined in male and female offspring born to mouse dams exposed to 0, 25, or 250 ng BPA/kg body weight per day from the evening of d 8 of gestation through d 16 of lactation. These studies examined the sexually dimorphic population of tyrosine hydroxylase (TH) neurons in the rostral periventricular preoptic area, an important brain region for estrous cyclicity and estrogen-positive feedback. The significant sex differences in TH neuron number observed in control offspring were diminished or obliterated in offspring exposed to BPA primarily because of a decline in TH neuron number in BPA-exposed females. As a functional endpoint of BPA action on brain sexual differentiation, we examined the effects of perinatal BPA exposure on sexually dimorphic behaviors in the open field. Data from these studies revealed significant sex differences in the vehicle-exposed offspring that were not observed in the BPA-exposed offspring. These data indicate that BPA may be capable…
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In certain behaviors, females appear to be more sensitive to the effects of BPA than males.
“BPA exposure, particularly when restricted to critical brain developmental periods, alters the sexually dimorphic brain and in certain behaviors, females appear to be more sensitive to the effects of BPA.”
From Gestational Exposure to Low Dose Bisphenol A Alters Social Behavior in Juvenile Mice (2011) · cites this paper as [11]
BPA exposure, particularly when restricted to critical brain developmental periods, alters the sexually dimorphic brain.
“BPA exposure, particularly when restricted to critical brain developmental periods, alters the sexually dimorphic brain and in certain behaviors, females appear to be more sensitive to the effects of BPA.”
From Gestational Exposure to Low Dose Bisphenol A Alters Social Behavior in Juvenile Mice (2011) · cites this paper as [11]
BPA exposure decreased the number of TH-positive cells in females, eliminating the sexual dimorphism in the AVPV of the hypothalamus.
“For example, BPA exposure decreased the number of tyrosine hydroxylase (TH) positive cells in females, eliminating the sexual dimorphism in the anteroventral periventricular region of the hypothalamus [11].”
From Gestational Exposure to Low Dose Bisphenol A Alters Social Behavior in Juvenile Mice (2011) · cites this paper as [11]
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- Authors
- Rubin, B. S., Lenkowski, J. R., Schaeberle, C. M., Vandenberg, L. N., Ronsheim, P. M., & Soto, A. M.
- Affiliations
- Tufts University (US)
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2006-08-01
- Volume
- 147
- Issue
- 8
- Pages
- 3681-3691
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2112484512
- Cited by
- 311
- References
- 5
- Citations by year
- 2025: 6 · 2024: 4 · 2023: 4 · 2022: 12 · 2021: 18 · 2020: 12 · 2019: 9 · 2018: 19 · 2017: 15 · 2016: 18 · 2015: 21 · 2014: 28 · 2013: 26 · 2012: 13
- FWCI
- 15.72
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- ScholarWorks@UMassAmherst (University of Massachusetts Amherst) (submittedVersion)
- Funders
- National Institute of Environmental Health Sciences (ES08314, R01ES008314)
- 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 › Sexual Differentiation and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- bisphenol A, perinatal exposure, sexual differentiation of the brain, tyrosine hydroxylase neurons, estrogenic endocrine disruptors, sex differences in behavior, estrous cyclicity, estrogen positive feedback, critical developmental periods, mouse offspring
- MeSH terms
- Bisphenol A Compounds, Animals, Arcuate Nucleus of Hypothalamus, Behavior, Animal, Benzhydryl Compounds, Cell Count, Critical Period, Psychological, Estrogens, Non-Steroidal, Exploratory Behavior, Female, Hypothalamus, Anterior, Male, Mice, Inbred Strains, Neurons, Paraventricular Hypothalamic Nucleus, Phenols, Pregnancy, Prenatal Exposure Delayed Effects, Preoptic Area, Septal Nuclei, Sexual Behavior, Animal, Sex Characteristics, Sexual Maturation, Tyrosine 3-Monooxygenase, Estrous Cycle, Mice
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