A novel model for neuroendocrine toxicology: neurobehavioral effects of BPA exposure in a prosocial species, the prairie vole (Microtus ochrogaster)
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Impacts on brain and behavior have been reported in laboratory rodents after developmental exposure to bisphenol A (BPA), raising concerns about possible human effects. Epidemiological data suggest links between prenatal BPA exposure and altered affective behaviors in children, but potential mechanisms are unclear. Disruption of mesolimbic oxytocin (OT)/vasopressin (AVP) pathways have been proposed, but supporting evidence is minimal. To address these data gaps, we employed a novel animal model for neuroendocrine toxicology: the prairie vole (Microtus ochrogaster), which are more prosocial than lab rats or mice. Male and female prairie vole pups were orally exposed to 5-μg/kg body weight (bw)/d, 50-μg/kg bw/d, or 50-mg/kg bw/d BPA or vehicle over postnatal days 8-14. Subjects were tested as juveniles in open field and novel social tests and for partner preference as adults. Brains were then collected and assessed for immunoreactive (ir) tyrosine hydroxylase (TH) (a dopamine marker) neurons in the principal bed nucleus of the stria terminalis (pBNST) and TH-ir, OT-ir, and AVP-ir neurons in the paraventricular nucleus of the hypothalamus (PVN). Female open field activity indicated hyperactivity at the lowest dose and anxiety at the highest dose. Effects on social interactions were also observed, and partner preference formation was mildly inhibited at all dose levels. BPA masculinized principal bed nucleus of the stria terminalis TH-ir neuron numbers in females. Additionally, 5…
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BPA exposure causes female-specific alteration of one-on-one social interactions in juvenile mice and prairie voles.
“as well as female-specific alteration of one-on-one social interactions in juvenile mice (Wolstenholme, 2011) and prairie voles (Sullivan et al., 2014).”
From The effects of prenatal PCBs on adult social behavior in rats (2015) · cites this paper as Sullivan et al., 2014
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 [62]
In prairie voles, females in the highest exposure group had fewer OT-ir neurons in the posterior PVN but more AVP-ir neurons in the anterior PVN.
“Females in the highest exposure group had fewer OT-ir neurons in the posterior PVN but more AVP-ir neurons in the anterior PVN.”
From Endocrine Disruption of Vasopressin Systems and Related Behaviors (2017) · cites this paper as [62]
Disruption of pBnST TH-ir neuron numbers occurred at the lowest dose, but not the higher two.
“Disruption of pBnST TH-ir neuron numbers also occurred at the lowest dose, but not the higher two making that outcome somewhat more difficult to interpret.”
From Endocrine Disruption of Vasopressin Systems and Related Behaviors (2017) · cites this paper as [62]
At the lower two doses, BPA eliminated the well-characterized sex difference in PVN TH-ir neuron numbers and reversed it at the highest dose.
“At the lower two doses, BPA eliminated the well-characterized sex difference in PVN TH-ir neuron numbers and reversed it at the highest dose.”
From Endocrine Disruption of Vasopressin Systems and Related Behaviors (2017) · cites this paper as [62]
At the two lower doses, BPA eliminated the sex difference in social investigation and at the highest dose, reversed it.
“At the two lower doses, BPA eliminated this sex difference and at the highest dose, reversed it.”
From Endocrine Disruption of Vasopressin Systems and Related Behaviors (2017) · cites this paper as [62]
Linkages between developmental BPA exposure and an anxiogenic phenotype have repeatedly been shown in dozens of studies using a variety of animal models and human populations.
“Nevertheless, linkages between developmental BPA exposure and an anxiogenic phenotype have repeatedly been shown in dozens of studies using a variety of animal models and human populations (representative examples include (62, 91, 93, 96–100)).”
From Endocrine Disruption of Vasopressin Systems and Related Behaviors (2017) · cites this paper as [62]
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- Authors
- Sullivan, A. W., Beach, E. C., Stetzik, L. A., Perry, A., D'Addezio, A. S., Cushing, B. S., & Patisaul, H. B.
- Affiliations
- North Carolina State University (US)
- University of Akron (US)
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2014-10-01
- Volume
- 155
- Issue
- 10
- Pages
- 3867-3881
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- PMC
- PMC6285157
- OpenAlex
- W2131055849
- Cited by
- 79
- References
- 24
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 7 · 2022: 5 · 2021: 15 · 2020: 5 · 2019: 8 · 2018: 8 · 2017: 13 · 2016: 6 · 2015: 7
- FWCI
- 5.70
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Endocrinology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- scholarworks - UTEP (The University of Texas at El Paso) (submittedVersion)
- Funders
- National Institute of Environmental Health Sciences (R21ES021233)
- Topics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Keywords
- bisphenol A, Microtus ochrogaster, oxytocin, vasopressin, mesolimbic system, mate preferences, social behavior, anxiety, hyperactivity, paraventricular nucleus, dopaminergic neurons, sex differences, prenatal exposure, developmental neurotoxicity, emotional behavior
- MeSH terms
- Bisphenol A Compounds, Affect, Animals, Behavior, Animal, Benzhydryl Compounds, Arvicolinae, Defense Mechanisms, Environmental Exposure, Environmental Pollutants, Female, Male, Motor Activity, Neurosecretory Systems, Phenols, Social Behavior, Toxicity Tests, Models, Animal, Endocrine Disruptors
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