Neonatal Exposure to Bisphenol A Alters Reproductive Parameters and Gonadotropin Releasing Hormone Signaling in Female Rats
Marina Fernández, Maria Bianchi,
Victoria Lux-Lantos and Carlos Libertun
doi: 10.1289/ehp.0800267 (available at http://dx.doi.org/)
Online 7 January 2009
ABSTRACT
Victoria Lux-Lantos and Carlos Libertun
doi: 10.1289/ehp.0800267 (available at http://dx.doi.org/)
Online 7 January 2009
ABSTRACT
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 μg/50μl (high), 50 μg/50μl (low) in castor oil, or vehicle. Westudied: body weight and age at vaginal opening, estrous cycles, pituitary hormone releasein vivo and in vitro, as well as gonadotropin releasing hormone (GnRH) pulsatility, atPND13 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 andGnRH-induced luteinizing hormone (LH), and increasing GnRH pulsatility. BPA dosedependentlyaccelerated 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-animalsshowed lower basal LH, dose-dependently affected GnRH-induced IP3 formation; thehigher dose also impaired GnRH-induced LH secretion. In addition, bothdoses alteredERK1/2 activation.
Conclusions: Neonatal exposure to BPA altered reproductive parameters and hypothalamicpituitaryfunction in female rats. To our knowledge, these results demonstrate for the firsttime that neonatal in vivo BPA permanently affects GnRH pulsatility and pituitary GnRHsignaling.
