Neonatal Exposure to Bisphenol A Alters Reproductive Parameters and Gonadotropin Releasing Hormone Signaling in Female Rats

FERNÁNDEZ M; BIANCHI M; LUX-LANTOS V; LIBERTUN C

ENVIRONMENTAL HEALTH PERSPECTIVES

National Institute of Environmental Health Sciences

Lugar: Research Triangre Park; Año: 2008

0091-6765

Background: Bisphenol A (BPA) is a component of polycarbonate plastics, epoxy resins and polystyrene found in many products. Several reports revealed potent in vivo effects, as BPA acts like an estrogen agonist and/or antagonist and androgen and thyroid hormone antagonist. Objectives: We analyzed the effects of neonatal exposure to BPA on the reproductive axis of female Sprague-Dawley rats. Methods: Females were injected subcutaneusly, daily, from postnatal day 1 (PND1) to PND10 with BPA, 500 ug/50ul (high), 50 ug/50ul (low) in castor oil, or vehicle. We studied: body weight and age at vaginal opening, estrous cycles, pituitary hormone release in vivo and in vitro, as well as gonadotropin releasing hormone (GnRH) pulsatility, at PND13 and in adults. We also analyzed GnRH-activated signaling pathways in adults: inositol-triphosphate (IP3), and extracellular signal-regulated kinase 1/2 (ERK1/2). Results: Exposure to BPA altered pituitary function in infantile rats, lowering basal and GnRH-induced luteinizing hormone (LH), and increasing GnRH pulsatility. BPA dose dependently accelerated puberty onset and altered estrous cyclicity, the high dose causing permanent estrus. In adults, neonatal BPA decreased GnRH-induced LH secretion in vivo, and GnRH pulsatility remained disrupted. In vitro, pituitary cells from BPA-animals showed lower basal LH, dose-dependently affected GnRH-induced IP3 formation; the higher dose also impaired GnRH-induced LH secretion. In addition, both doses altered ERK1/2 activation. Conclusions: Neonatal exposure to BPA altered reproductive parameters and hypothalamic pituitary function in female rats. To our knowledge, these results demonstrate for the first time that neonatal in vivo BPA permanently affects GnRH pulsatility and pituitary GnRH signaling.