Cited by 86Effects and risks of endocrine disrupting chemicalsSexual Differentiation and DisordersHypothalamic control of reproductive hormones

The impact of neonatal bisphenol-A exposure on sexually dimorphic hypothalamic nuclei in the female rat

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Adewale, Heather B., Todd, Karina L., Mickens, Jillian A., Patisaul, Heather B.·2011·NeuroToxicology

Abstract

Now under intense scrutiny, due to its endocrine disrupting properties, the potential threat the plastics component bisphenol-A (BPA) poses to human health remains unclear. Found in a multitude of polycarbonate plastics, food and beverage containers, and medical equipment, BPA is thought to bind to estrogen receptors (ERs), thereby interfering with estrogen-dependent processes. Our lab has previously shown that exposure to BPA (50mg/kg bw or 50μg/kg bw) during the neonatal critical period is associated with advancement of puberty, early reproductive senescence and ovarian malformations in female Long Evans rats. Here, using neural tissue obtained from the same animals, we explored the impact of neonatal BPA exposure on the development of sexually dimorphic hypothalamic regions critical for female reproductive physiology and behavior. Endpoints included quantification of oxytocin-immunoreactive neurons (OT-ir) in the paraventricular nucleus (PVN), serotonin (5-HT-ir) fiber density in the ventrolateral subdivision of the ventromedial nucleus (VMNvl) as well as ERα-ir neuron number in the medial preoptic area (MPOA), the VMNvl, and the arcuate nucleus (ARC). Both doses of BPA increased the number of OT-ir neurons within the PVN, but no significant effects were seen on 5-HT-ir fiber density or ERα-ir neuron number in any of the areas analyzed. In addition to hypothalamic development, we also assessed female sex behavior and body weight. No effect of BPA on sexual receptivity or proceptive behavior in females was observed. Females treated with BPA, however, weighed significantly more than control females by postnatal day 99. This effect of BPA on weight is critical because alterations in metabolism, are frequently associated with reproductive dysfunction. Collectively, the results of this and our prior study indicate that the impact of neonatal BPA exposure within the female rat hypothalamus is region specific and support the hypothesis that developmental BPA exposure may adversely affect reproductive development in females.

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Crossref · 10.1016/j.neuro.2010.07.008

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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 [61]

    The Results (section 3.3) report that neonatal BPA exposure increased OT neuron numbers in the rostral PVN of female rats. The paper does not report BPA-induced changes in AVP neurons or innervation, or establish these neural effects or anxiogenic effects in multiple species; the Discussion (section 4.1) says the physiological and behavioral significance of the OT finding remains unclear. Page numbers were not available in our copy. (LLM, conf=0.88)

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  • Neonatal exposure to BPA (50 mg/kg bw or 50 μg/kg bw) by subcutaneous injection can alter the number of PVN OT immunolabeled cells in adulthood in female rats.

    “In a separate study, we showed that that neonatal exposure to BPA (50 mg/kg bw or 50 µg/kg bw) by subcutaneous injection can alter the number of PVN OT immunolabeled cells in adulthood (in female rats) (61).”
  • Exposure significantly increased OT-immunoreactive neuron numbers, but only in the anterior PVN.

    “Exposure significantly increased OT-immunoreactive (-ir) neuron numbers, but only in the anterior PVN, a result interpreted to potentially indicate sequestration of OT and reduced release from nerve terminals.”

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3 of the 135 references couldn’t be matched to a known paper.

Research works printed but not linked: 4

  1. Khurana S Ranmal S Ben-Jonathan N Exposure of newborn male and female rats to environmental estrogens: delayed and sustained hyperprolactinemia and alterations in estrogen receptor expression Endocrinology 2000 141 4512 7 11108262
  2. Ryan KK Haller AM Sorrell JE Woods SC Jandacek RJ Seeley RJ Perinatal Exposure to Bisphenol-A and the Development of Metabolic Syndrome in CD-1 Mice Endocrinology 2010c PMC2875828 20351315
  3. Shughrue PL Lane MV Merchenthaler I Comparative distribution of estrogen receptor α and β mRNA in the rat central nervous system Journal of Comparative Neurology 1997 388 507 25 9388012
  4. Wallen K Hormonal influences on sexually differentiated behavior in nonhuman primates Front Neuroendocrinol 2005b 26 7 26 15862182

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Authors
Adewale, H. B., Todd, K. L., Mickens, J. A., & Patisaul, H. B.
Affiliations
North Carolina State University (US)
Corresponding author
Patisaul, Heather B.
Venue
NeuroToxicology
Publisher
Elsevier BV
Published
2011-01
Volume
32
Issue
1
Pages
38-49
ISSN
0161-813X (ISSN-L)
OpenAlex
W2071994059
Cited by
86
References
135
Citations by year
2025: 2 · 2023: 3 · 2022: 3 · 2021: 8 · 2020: 5 · 2019: 7 · 2018: 7 · 2017: 7 · 2016: 7 · 2015: 8 · 2014: 7 · 2013: 8 · 2012: 3
FWCI
5.14
Type
journal article
Language
en
Open access
Locations
  • NeuroToxicology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
NIEHS (RO1ES016001)
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
  • Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
Keywords
bisphenol A, endocrine disruptors, neonatal exposure, hypothalamus, sexual dimorphism, estrogen receptor alpha, oxytocin neurons, paraventricular nucleus, serotonin, ventromedial hypothalamus, medial preoptic area, arcuate nucleus, female reproductive development, puberty, weight gain, female sexual behavior, Long-Evans rats
MeSH terms
Bisphenol A Compounds, Age Factors, Animals, Animals, Newborn, Arcuate Nucleus of Hypothalamus, Benzhydryl Compounds, Body Weight, Female, Phenols, Preoptic Area, Sexual Behavior, Animal, Sex Characteristics, Ventromedial Hypothalamic Nucleus, Rats, Long-Evans, Rats

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