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Cited by 106Effects and risks of endocrine disrupting chemicalsPhytoestrogen effects and researchEstrogen and related hormone effects

Anxiogenic effects of developmental bisphenol A exposure are associated with gene expression changes in the juvenile rat amygdala and mitigated by soy

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Patisaul, Heather B., Sullivan, Alana W., Radford, Meghan E., Walker, Deena M., Adewale, Heather B., Winnik, Bozena, Coughlin, Janis L., Buckley, Brian +1 more·2012·PLoS ONE
DOI 10.1371/journal.pone.0043890PMC PMC3434201
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Abstract

Early life exposure to Bisphenol A (BPA), a component of polycarbonate plastics and epoxy resins, alters sociosexual behavior in numerous species including humans. The present study focused on the ontogeny of these behavioral effects beginning in adolescence and assessed the underlying molecular changes in the amygdala. We also explored the mitigating potential of a soy-rich diet on these endpoints. Wistar rats were exposed to BPA via drinking water (1 mg/L) from gestation through puberty, and reared on a soy-based or soy-free diet. A group exposed to ethinyl estradiol (50 µg/L) and a soy-free diet was used as a positive estrogenic control. Animals were tested as juveniles or adults for anxiety-like and exploratory behavior. Assessment of serum BPA and genistein (GEN), a soy phytoestrogen, confirmed that internal dose was within a human-relevant range. BPA induced anxiogenic behavior in juveniles and loss of sexual dimorphisms in adult exploratory behavior, but only in the animals reared on the soy-free diet. Expression analysis revealed a suite of genes, including a subset known to mediate sociosexual behavior, associated with BPA-induced juvenile anxiety. Notably, expression of estrogen receptor beta (Esr2) and two melanocortin receptors (Mc3r, Mc4r) were downregulated. Collectively, these results show that behavioral impacts of BPA can manifest during adolescence, but wane in adulthood, and may be mitigated by diet. These data also reveal that, because ERβ and melanocortin receptors are crucial to their function, oxytocin/vasopressin signaling pathways, which have previously been linked to human affective disorders, may underlie these behavioral outcomes.

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  • BPA 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 [60]

    The Discussion (page unavailable) reports anxiogenic effects of developmental BPA exposure in this rat study and cites similar findings in two mouse species. It discusses oxytocin and vasopressin signaling as a possible mechanism, but does not report altered AVP or OT neuron numbers or innervation of sexually dimorphic regions; it says their gene expression was not significantly altered in the amygdala. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Wistar rats perinatally exposed to BPA via drinking water [1 mg/L] displayed elevated anxiety-related behaviors as juveniles.

    “In a study done in collaboration with Andrea Gore’s laboratory, we found that Wistar rats perinatally exposed to BPA via drinking water [1 mg/L; a dosing regimen that resulted in serum levels approximately equivalent to humans (94)], displayed elevated anxiety-related behaviors as juveniles (60).”

    From Endocrine Disruption of Vasopressin Systems and Related Behaviors (2017) · cites this paper as [60]

    The Methods (Animal Care and Exposure) describe Wistar rats exposed to BPA in drinking water at 1 mg/L from gestation through postnatal day 40. The Results (Juvenile Exploratory and Anxiety-like Behavior) report anxiety-related behavior in BPA-exposed juveniles on the soy-free diet, but also report that a soy-based diet mitigated the effect. The claim omits that dietary qualification. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Consumption of a soy-rich diet ameliorated the behavioral effects of BPA to some degree.

    “Consumption of a soy-rich diet, which is hormonally active and contains estrogenic phytoestrogens including GEN, ameliorated the behavioral effects to some degree.”

    From Endocrine Disruption of Vasopressin Systems and Related Behaviors (2017) · cites this paper as [60]

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Cited by

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Authors
Patisaul, H. B., Sullivan, A. W., Radford, M. E., Walker, D. M., Adewale, H. B., Winnik, B., Coughlin, J. L., Buckley, B., & Gore, A. C.
Affiliations
  • North Carolina State University (US)
  • The University of Texas at Austin (US)
  • Rutgers, The State University of New Jersey (US)
  • Environmental and Occupational Health Sciences Institute (US)
Corresponding author
Patisaul, Heather B.
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2012-09-05
Volume
7
Issue
9
Pages
e43890
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0043890
PMC
PMC3434201
OpenAlex
W2025397596
Cited by
106
References
11
Citations by year
2026: 2 · 2025: 2 · 2024: 3 · 2023: 3 · 2022: 4 · 2021: 7 · 2020: 9 · 2019: 8 · 2018: 12 · 2017: 7 · 2016: 10 · 2015: 17 · 2014: 14 · 2013: 8
FWCI
8.66
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Rutgers University Community Repository (Rutgers University) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
  • National Institutes of Health (5r01es020662-05)
  • National Institute on Aging (F31AG034813, AG034813)
  • National Institute of Environmental Health Sciences (ES020662, #ES07784, R01ES016001, R01-ES020662, R21ES021233, ES-05022., ES018139, P30ES007784, R56ES020662, ES16001, RC1ES018139, T32ES007148, P30ES005022)
Topics
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Phytoestrogen effects and research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
Keywords
bisphenol A, anxiety-like behavior, soy-based diet, genistein, estrogen receptor beta, melanocortin receptors, melanocortin 3 receptor, melanocortin-4 receptor, exploratory behavior, sexual dimorphism, sociosexual behavior, puberty, ethinyl estradiol, endocrine disruptors
MeSH terms
Bisphenol A Compounds, Amygdala, Animals, Anxiety, Benzhydryl Compounds, Female, Phenols, Pregnancy, Pregnancy, Animal, Sex Characteristics, Glycine max, Water, Rats, Wistar, Maternal Exposure, Genistein, Gene Expression Profiling, Receptors, Melanocortin, Estrogen Receptor beta, Rats

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