Neonatal exposure to bisphenol a and reproductive and endocrine alterations resembling the polycystic ovarian syndrome in adult rats.

摘要

BACKGROUND: Bisphenol A (BPA), an endocrine disruptor, is a component of polycarbonate plastics, epoxy resins, and polystyrene. Several studies have reported potent in vivo effects, because BPA behaves as an estrogen agonist and/or antagonist and as an androgen and thyroid hormone antagonist. OBJECTIVES: We investigated the effects of neonatal exposure to BPA on the reproductive axis in adult female Sprague-Dawley rats. METHODS: Female rats were injected subcutaneously, daily from postnatal day 1 (PND1) to PND10 with BPA in castor oil at 500 microg/50 microL [BPA500; approximately 10-4 M, a dose higher than the lowest observed adverse effect level (LOAEL) of 50 mg/kg], 50 microg/50 microL (BPA50), or 5 microg/50 microL (both BPA50 and BPA5 are doses lower than the LOAEL), or castor oil vehicle alone. In adults we studied a) the release of gonadotropin-releasing hormone (GnRH) from hypothalamic explants, b) serum sex hormone levels, and c) ovarian morphology, ovulation, and fertility. RESULTS: Neonatal exposure to BPA was associated with increased serum testosterone and estradiol levels, reduced progesterone in adulthood, and altered in vitro GnRH secretion. Animals exposed to BPA500 had altered ovarian morphology, showing a large number of cysts. Animals exposed to BPA50 had reduced fertility without changes in the number of oocytes on the morning of estrus, whereas animals exposed to BPA500 showed infertility. CONCLUSIONS: Exposure to high doses of BPA during the period of brain sexual differentiation altered the hypothalamic-pituitary-gonadal axis in female Sprague-Dawley rats. These results have the potential to link neonatal exposure to high doses of BPA in rats with the development of polycystic ovarian syndrome. Studies of doses and routes of administration more consistent with human exposures are needed to determine the relevance of these findings to human health.