Multi- and transgenerational consequences of bisphenol A on sexually dimorphic cell populations in mouse brain
Open accessAbstract
Bisphenol A (BPA) is an endocrine-disrupting compound used to manufacture plastics; it is present in linings of food cans, bottles, thermal receipts, and many other everyday items and is detectable in human urine and blood. Exposure to BPA during development can disrupt sexual differentiation of some brain regions. Moreover, BPA can have transgenerational effects on gene expression and behaviors. Here, we used a diet and breeding regimen that produces transgenerational effects on behaviors. C57BL/6J mice consumed control or BPA-containing diets during pregnancy. We examined vasopressin (AVP) and estrogen receptor α (ERα) immunoreactivity (ir) in sexually dimorphic brain regions from first-generation (F1) offspring and transgenerational effects of BPA in third-generation offspring. In all but one brain region examined, the expected sex differences were noted in both generations of control mice. In F1 mice, a diet by sex interaction was present for AVP-ir in the lateral septum and posterodorsal medial amygdala. In both regions, BPA exposure reduced immunoreactivity in male brains. An interaction between diet and sex for ERα-ir in the ventromedial hypothalamus was caused by reduced immunoreactivity in BPA-exposed females. Of interest, BPA had transgenerational effects on ERα-ir in the anteroventral periventricular nucleus and bed nucleus of the stria terminalis. Our data show that BPA produces immunoreactive differences in ERα-ir generations after exposure to BPA. We speculate that actions of BPA in utero on ERα-ir in brain have long-term consequences for reproduction and social behavior.
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No evidence of disrupted AVP-ir levels was found for the MePD, PVN, LS or BnST in BPA-exposed mice.
“No evidence of disrupted AVP-ir levels was found for the MePD, PVN, LS or BnST (66).”
From Endocrine Disruption of Vasopressin Systems and Related Behaviors (2017) · cites this paper as [66]
The Results (AVP-ir in F1 brains; page not provided) report reduced AVP immunoreactivity in the MePD after gestational BPA exposure and decreased immunoreactive area in BPA-exposed males in both the MePD and LS. Thus the claim that no disruption was found in any of the four regions contradicts the F1 findings, even though the Results for F3 brains report no diet main effects in those regions. (LLM, conf=0.90)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredBPA alters AVP and OT neuron numbers and innervation of sexually dimorphic regions associated with social and aggressive behaviors in multiple species, and is anxiogenic in multiple species.
“Altered AVP and OT neuron numbers and innervation of sexually dimorphic regions associated with social and aggressive behaviors in multiple species; anxiogenic in multiple species”
From Endocrine Disruption of Vasopressin Systems and Related Behaviors (2017) · cites this paper as [66]
The Results (AVP-ir in F1 brains; page unavailable) report reduced AVP immunoreactivity in sexually dimorphic regions of BPA-exposed male mice, and the Discussion links the AVP circuit to social behavior. The Methods (Image analysis; page unavailable) specify that immunoreactive area was measured without distinguishing cells from fibers. The paper does not establish altered OT neuron numbers or innervation, aggressive behavior, or anxiogenic effects in multiple species; its BPA findings here are primarily in mice. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIn the transgenerational mouse model, disrupted ERα-ir was found in F3 females from the BPA-exposed lineage, with higher levels in the AVPV and lower levels in the BnST.
“Moreover, in the transgenerational mouse model, one of the most striking findings was disrupted ERα-ir in the F3 females from the BPA-exposed lineage, with higher levels in the AVPV and lower levels in the BnST (66).”
From Endocrine Disruption of Vasopressin Systems and Related Behaviors (2017) · cites this paper as [66]
F1 male mice exposed to BPA had fewer AVP-ir in the MePD than unexposed males, while females were unaffected.
“F1 males had fewer AVP-ir in the MePD than unexposed males, but females were unaffected.”
From Endocrine Disruption of Vasopressin Systems and Related Behaviors (2017) · cites this paper as [66]
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- Authors
- Goldsby, J. A., Wolstenholme, J. T., & Rissman, E. F.
- Affiliations
- University of Virginia (US)
- North Carolina State University (US)
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2016-11-14
- Volume
- 158
- Issue
- 1
- Pages
- 21-30
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- PMC
- PMC5412975
- OpenAlex
- W2553518712
- Cited by
- 48
- References
- 38
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 3 · 2023: 4 · 2022: 5 · 2021: 4 · 2020: 7 · 2019: 4 · 2018: 7 · 2017: 5
- FWCI
- 3.35
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Endocrinology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Virginia
- National Institutes of Health
- National Institute of Environmental Health Sciences (R01ES022759, F32ES019404)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P50HD028934)
- 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
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Keywords
- bisphenol A, endocrine disruptors, transgenerational effects, prenatal exposure, sexual differentiation of the brain, vasopressin, estrogen receptor alpha, lateral septum, posterodorsal medial amygdala, ventromedial hypothalamus, anteroventral periventricular nucleus, bed nucleus of the stria terminalis, social behavior, reproduction
- MeSH terms
- Bisphenol A Compounds, Amygdala, Animals, Benzhydryl Compounds, Brain, Female, Mice, Inbred C57BL, Phenols, Pregnancy, Prenatal Exposure Delayed Effects, Random Allocation, Septal Nuclei, Sex Characteristics, Vasopressins, Estrogen Receptor alpha, Mice, Endocrine Disruptors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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