Neonatal Treatment with Bisphenol A alters Reproductive Parameters in the pre and postpubertal female rat

FERNANDEZ MARINA; LUX-LANTOS VICTORIA; LIBERTUN CARLOS

San Francisco, USA

Congreso; The Endocrine Society's 90th Annual Meeting; 2008

The Endocrine Society

Bisphenol A, 2, 2-bis (4-hydroxyphenyl) propane, (BPA), is an estrogenic endocrine disruptor that alters normal functions in several species, including rats and humans. In this work we studied the effect of the neonatal administration of this xenoestrogen in female rats on pre and postpubertal reproductive parameters. Female Sprague-Dawley rats were injected sc, daily from postnatal days (PND)1 to 10 with BPA: 500 µg/50 µl oil (H), or 50 µg/50 µl oil (L), or vehicle as control (C). We studied: body weight (BW), age at vaginal opening, estrous cycles and pituitary LH release in vivo and in vitro at PND13 and adults. For the in vivo tests, PND13 animals were killed by decapitation 15 min after an ip injection of 100 ng GnRH, whereas in adults, under ketamine/xylazine anesthesia (60/10 mg/kg BW), blood samples were taken basally and after 15 and 50 min of intrajugular injection of 100 ng GnRH from the jugular vein. Serum LH was analyzed by RIA. For the in vitro tests primary pituitary cultures (PPC) were performed as in (1) from PND13 and adult females. After 4 days in culture, cells were stimulated for 60 min with GnRH (1.10-9-1.10-7) in the PND13-PPC or for 5, 10, 15, or 30 min with GnRH 1.10-7 M in the adult PPC and medium LH determined. ERK1/2 activation was analyzed in the adult PPC by Western Blot as in (2). BPA-pretreated animals opened vagina earlier than controls (days: H 30.2±0.6; L 32.6±0.7; C 34.9±0.7; p<0.05). H rats showed irregular cycles with high prevalence of estrus (% of estrus: H 99.2±0.8; L 25.8±2.7; C 25.5±1.3, p<0.05 H vs. C). In PND13 rats both basal and GnRH-stimulated serum LH was lower in H than in C, p<0.05. In adults, basal LH was similar among groups while GnRH-stimulated release was lower in H at 15 min [(ng/ml): H 16.2±1.8; L 21.9±4.2; C 25.6±3.8, H vs. C p< 0.05]. In vivo BPA pretreatment diminished LH release in PND13-PPC, but did not modify the response to GnRH. In contrast, in adult PPC BPA-pretreated groups released less LH both basally and after GnRH (p<0.05); H failed to respond to GnRH, whereas L and C showed an increase in LH at 10 minutes (p<0.05). ERK1/2 phosphorylation was rapid and sustained in C, whereas in H and L it was transient, with the highest level observed at 5 min. At this time-point H showed significantly lower pERK1/2 levels than C (p<0.05). We conclude that neonatal in vivo BPA treatment has marked effects on the hypothalamic-pituitary-ovarian axis in female rats.    1.   Bianchi, M. S., Catalano, P. N., Bonaventura, M. M., Silveyra, P., Bettler, B., Libertun, C., and Lux-Lantos, V. A. (2004) Neuroendocrinology 80, 129-142    2.   Chamson-Reig, A., Sorianello, E., Catalano, P. N., Fernández, M. O., Pignataro, O. P., Libertun, C., and Lux-Lantos, V. A. R. (2003) Endocrinology 144, 2957-2966