NEONATAL EXPOSURE TO BISPHENOL A INDUCES ENDOCRINE DISORDERS AND ALTERS GnRH PULSATILITY IN INFANTILE AND ADULT FEMALE RATS.

FERNANDEZ MO; BOURGUIGNON NS; LUX LANTOS VAR; LIBERTUN C

Washington

Congreso; The Endocrine Society's 91st Annual Meeting; 2009

The Endocrine Society

Neonatal Exposure to Bisphenol A induces endocrine disorders and alters GnRH pulsatility in infantile and adult female rats. MO Fernández 1,2, NS Bourguignon1, VAR Lux Lantos 1 and C Libertun 1,2. 1Instituto de Biología y Medicina Experimental-CONICET, 2 Facultad de  Medicina, Universidad de Buenos Aires, Argentina. Previously we showed that animals neonatally exposed to Bisphenol A (BPA) exhibited precocious puberty, altered pituitary response to GnRH and estrous cyclicity. In this study, we analyzed the effects of neonatal exposure to BPA on the pulsatile release of GnRH on postnatal day (PND) 13 and in adults (120 days old), and on serum hormones and ovarian weight (OW) in adults. Female Sprague-Dawley rats were injected sc, daily from PND1 to PND10 with BPA: 500 µg/50 µl oil (H), or 50 µg/50 µl oil (M), or, in same cases, 5 µg/50 µl (L), or, vehicle as control (C). We studied: Pulsatile release of GnRH in PND13 and adults: Hypothalamic explants were incubated for 6 h in Krebs-Ringer (37 ºC), the medium renewed at 9-min intervals. GnRH was measured (RIA) and the results analyzed using Cluster8. In adults: we determined OW, and serum estradiol (E2), progesterone (P4), testosterone (T) and PRL (RIA). For all studies in adults, animals were used in the morning of estrus. PND13 BPA-exposed animals showed increased GnRH pulse frequency [peaks/hour: C 0.46±0.04; L 0.83±0.10; M 0.75±0.05; H 0.79±0.04, C vs BPA p<0.05, n=4] and decreased interpulse intervals (IPI) [IPI (min): C 75.9± 5.5; L 54.9±7.8; M 60.4±1.4; H 55.7±3.1, C vs BPA p<0.05, n=4]. Adults neonatally exposed to BPA also showed increased GnRH pulse frequency (p<0.05). Ovaries from M and H were smaller than C [OW (mg): C 143.2±10.8; M 119.7±4.0; H 87.0±7.2, C vs BPA p<0.05, n=6]. Serum E2 and T were significantly augmented in M and H (p<0.05), whereas P4 was significantly reduced in L, M and H (p<0.05). Serum PRL was significantly higher in H [PRL (ng/ml): C 4.34±0.67; M 5.42±0.66; H 11.34±1.31, C vs H p<0.05, n=8]. Neonatal exposure to BPA induced increased GnRH pulse frequency in PND13, evidence of precocious hypothalamic maturation. Adults neonatally exposed to BPA also showed increased GnRH pulse frequency, revealing that the alterations persisted in adult life, long after the exposure to BPA ceased. In addition, adults neonatally exposed to H and M showed ovarian alterations, and all BPA animals exhibited altered serum steroid hormone levels. H also showed hyperprolactinemia, possibly contributing to the alterations in cyclicity observed previously. These results show that exposure to BPA during the neonatal period alters irreversibly reproductive parameters in female rats. Exposure to this agent could contribute to the development of many endocrine disorders of increased incidence among human population. Supported by CONICET, ANPCyT (BID 1728/OC-AR PICT 2004 05–26307 to CL and PICT 2006 Nº 00200 to VLL) and UBA. Authors have nothing to disclose Este trabajo obtuvo el Abstract Travel Grant, The Endocrine Society