Disrupted organization of RFamide pathways in the hypothalamus is associated with advanced puberty in female rats neonatally exposed to bisphenol A.

Biology of Reproduction
Sandra M Losa-WardH B Patisaul

Abstract

Hypothalamic neurons, which produce the kisspeptin family of peptide hormones (Kp), are critical for initiating puberty and maintaining estrous cyclicity by stimulating gonadotropin-releasing hormone (GnRH) release. Conversely, RFamide-related peptide-3 (RFRP3) neurons inhibit GnRH activity. It has previously been shown that neonatal exposure to bisphenol A (BPA) can alter the timing of female pubertal onset and induce irregular estrous cycles or premature anestrus. Here we tested the hypothesis that disrupted ontogeny of RFamide signaling pathways may be a mechanism underlying advanced puberty. To test this, we used a transgenic strain of Wistar rats whose GnRH neurons express enhanced green fluorescent protein. Pups were exposed by daily subcutaneous injection to vehicle, 17beta-estradiol (E2), 50 μg/kg BPA, or 50 mg/kg BPA, from Postnatal Day (PND) 0 through PND 3, and then cohorts were euthanized on PNDs 17, 21, 24, 28, and 33 (5-8 animals per age per exposure; males were collected on PNDs 21 and 33). Vaginal opening was advanced by E2 and 50 μg/kg BPA. On PND 28, females exposed to E2 and 50 μg/kg BPA had decreased RFRP-3 fiber density and contacts on GnRH neurons. RFRP3 perikarya were also decreased in females exposed to ...Continue Reading

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Citations

Jan 10, 2014·The Journal of Endocrinology·Lydie NauléSakina Mhaouty-Kodja
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Nov 9, 2018·Frontiers in Neuroscience·Takayoshi Ubuka, Kazuyoshi Tsutsui
Dec 9, 2020·Nature Reviews. Endocrinology·David Lopez-RodriguezAnne-Simone Parent
Jul 3, 2021·International Journal of Environmental Research and Public Health·Donatella CasertaIlary Ruscito
Feb 8, 2019·Neuroendocrinology·Carlos Francisco AylwinAlejandro Lomniczi

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Methods Mentioned

BETA
transgenic
lavage
confocal microscopy

Software Mentioned

ImageJ
Image J

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