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

Sandra M. Losa-Ward, Karina L. Todd, Katherine A. McCaffrey, Kazuyoshi Tsutsui, Heather B. Patisaul*

*この研究の対応する著者

    研究成果: Article査読

    60 被引用数 (Scopus)

    抄録

    Hypothalamic neurons, which produce the kisspeptin family of peptide hormones (Kp), are critical for initiating puberty and maintaining estrous cyclicity by stimulating gonadotropinreleasing 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, 17betaestradiol (E2), 50 lg/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 lg/kg BPA. On PND 28, females exposed to E2 and 50 lg/kg BPA had decreased RFRP-3 fiber density and contacts on GnRH neurons. RFRP3 perikarya were also decreased in females exposed to 50 lg/kg BPA. Data suggest that BPA-induced premature puberty results from decreased inhibition of GnRH neurons.

    本文言語English
    論文番号Article 28
    ジャーナルBiology of Reproduction
    87
    2
    DOI
    出版ステータスPublished - 2012 8月 1

    ASJC Scopus subject areas

    • 細胞生物学

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