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

    Research output: Contribution to journalArticle

    47 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Article numberArticle 28
    JournalBiology of Reproduction
    Volume87
    Issue number2
    DOIs
    Publication statusPublished - 2012 Aug 1

    Keywords

    • Endocrine disruptor
    • Kisspeptin
    • Puberty
    • RFRP

    ASJC Scopus subject areas

    • Cell Biology

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