Neonatal Exposure to Bisphenol A and Reproductive and Endocrine Alterations Resembling the Polycystic Ovarian Syndrome in Adult Rats

FERNANDEZ MO; BOURGUIGNON NS; LUX-LANTOS VA; LIBERTUN C

ENVIRONMENTAL HEALTH PERSPECTIVES

US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE

Lugar: Research Triangle Park, NC. USA; Año: 2010 vol. 118 p. 1217 - 1222

0091-6765

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, as BPA acts like an estrogen agonist and/or antagonist and androgen and thyroid hormone antagonist. Objectives: We investigated the effects of neonatal exposure to BPA on the reproductive axis in adult Sprague-Dawley females. Methods: Females were injected subcutaneously, daily, from postnatal day 1 (PND1) to PND10 with BPA, 500 ìg/50ìl (BPA500, ~10-4 M, a dose higher than the LOAEL=50 mg/kg), 50 ìg/50ìl (BPA50), 5 ìg/50ìl (BPA5) in castor oil (both doses lower than the LOAEL) or vehicle. We studied in adults: GnRH release from hypothalamic explants, serum sexual hormone levels, ovarian morphology, ovulation and fertility. Results: Neonatal exposure to BPA was associated with increased serum testosterone and estradiol levels and reduced progesterone in adulthood, and with 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 Sprague-Dawley females. These results have the potential to link the neonatal exposure to high doses of BPA in rats with the development of PCOS. Studies of doses and routes of administration more consistent with human exposures are needed to determine the relevance of these findings to human health. 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 Sprague-Dawley females. These results have the potential to link the neonatal exposure to high doses of BPA in rats with the development of PCOS. Studies of doses and routes of administration more consistent with human exposures are needed to determine the relevance of these findings to human health. ìg/50ìl (BPA50), 5 ìg/50ìl (BPA5) in castor oil (both doses lower than the LOAEL) or vehicle. We studied in adults: GnRH release from hypothalamic explants, serum sexual hormone levels, ovarian morphology, ovulation and fertility. Results: Neonatal exposure to BPA was associated with increased serum testosterone and estradiol levels and reduced progesterone in adulthood, and with 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 Sprague-Dawley females. These results have the potential to link the neonatal exposure to high doses of BPA in rats with the development of PCOS. Studies of doses and routes of administration more consistent with human exposures are needed to determine the relevance of these findings to human health. 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 Sprague-Dawley females. These results have the potential to link the neonatal exposure to high doses of BPA in rats with the development of PCOS. Studies of doses and routes of administration more consistent with human exposures are needed to determine the relevance of these findings to human health. BPA acts like an estrogen agonist and/or antagonist and androgen and thyroid hormone antagonist. Objectives: We investigated the effects of neonatal exposure to BPA on the reproductive axis in adult Sprague-Dawley females. Methods: Females were injected subcutaneously, daily, from postnatal day 1 (PND1) to PND10 with BPA, 500 ìg/50ìl (BPA500, ~10-4 M, a dose higher than the LOAEL=50 mg/kg), 50 ìg/50ìl (BPA50), 5 ìg/50ìl (BPA5) in castor oil (both doses lower than the LOAEL) or vehicle. We studied in adults: GnRH release from hypothalamic explants, serum sexual hormone levels, ovarian morphology, ovulation and fertility. Results: Neonatal exposure to BPA was associated with increased serum testosterone and estradiol levels and reduced progesterone in adulthood, and with 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 Sprague-Dawley females. These results have the potential to link the neonatal exposure to high doses of BPA in rats with the development of PCOS. Studies of doses and routes of administration more consistent with human exposures are needed to determine the relevance of these findings to human health. 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 Sprague-Dawley females. These results have the potential to link the neonatal exposure to high doses of BPA in rats with the development of PCOS. Studies of doses and routes of administration more consistent with human exposures are needed to determine the relevance of these findings to human health. ìg/50ìl (BPA50), 5 ìg/50ìl (BPA5) in castor oil (both doses lower than the LOAEL) or vehicle. We studied in adults: GnRH release from hypothalamic explants, serum sexual hormone levels, ovarian morphology, ovulation and fertility. Results: Neonatal exposure to BPA was associated with increased serum testosterone and estradiol levels and reduced progesterone in adulthood, and with 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 Sprague-Dawley females. These results have the potential to link the neonatal exposure to high doses of BPA in rats with the development of PCOS. Studies of doses and routes of administration more consistent with human exposures are needed to determine the relevance of these findings to human health. 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 Sprague-Dawley females. These results have the potential to link the neonatal exposure to high doses of BPA in rats with the development of PCOS. Studies of doses and routes of administration more consistent with human exposures are needed to determine the relevance of these findings to human health. in vivo effects, as BPA acts like an estrogen agonist and/or antagonist and androgen and thyroid hormone antagonist. Objectives: We investigated the effects of neonatal exposure to BPA on the reproductive axis in adult Sprague-Dawley females. Methods: Females were injected subcutaneously, daily, from postnatal day 1 (PND1) to PND10 with BPA, 500 ìg/50ìl (BPA500, ~10-4 M, a dose higher than the LOAEL=50 mg/kg), 50 ìg/50ìl (BPA50), 5 ìg/50ìl (BPA5) in castor oil (both doses lower than the LOAEL) or vehicle. We studied in adults: GnRH release from hypothalamic explants, serum sexual hormone levels, ovarian morphology, ovulation and fertility. Results: Neonatal exposure to BPA was associated with increased serum testosterone and estradiol levels and reduced progesterone in adulthood, and with 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 Sprague-Dawley females. These results have the potential to link the neonatal exposure to high doses of BPA in rats with the development of PCOS. Studies of doses and routes of administration more consistent with human exposures are needed to determine the relevance of these findings to human health. 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 Sprague-Dawley females. These results have the potential to link the neonatal exposure to high doses of BPA in rats with the development of PCOS. Studies of doses and routes of administration more consistent with human exposures are needed to determine the relevance of these findings to human health. ìg/50ìl (BPA50), 5 ìg/50ìl (BPA5) in castor oil (both doses lower than the LOAEL) or vehicle. We studied in adults: GnRH release from hypothalamic explants, serum sexual hormone levels, ovarian morphology, ovulation and fertility. Results: Neonatal exposure to BPA was associated with increased serum testosterone and estradiol levels and reduced progesterone in adulthood, and with 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 Sprague-Dawley females. These results have the potential to link the neonatal exposure to high doses of BPA in rats with the development of PCOS. Studies of doses and routes of administration more consistent with human exposures are needed to determine the relevance of these findings to human health. 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 Sprague-Dawley females. These results have the potential to link the neonatal exposure to high doses of BPA in rats with the development of PCOS. Studies of doses and routes of administration more consistent with human exposures are needed to determine the relevance of these findings to human health. -4 M, a dose higher than the LOAEL=50 mg/kg), 50 ìg/50ìl (BPA50), 5 ìg/50ìl (BPA5) in castor oil (both doses lower than the LOAEL) or vehicle. We studied in adults: GnRH release from hypothalamic explants, serum sexual hormone levels, ovarian morphology, ovulation and fertility. Results: Neonatal exposure to BPA was associated with increased serum testosterone and estradiol levels and reduced progesterone in adulthood, and with 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 Sprague-Dawley females. These results have the potential to link the neonatal exposure to high doses of BPA in rats with the development of PCOS. Studies of doses and routes of administration more consistent with human exposures are needed to determine the relevance of these findings to human health. 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 Sprague-Dawley females. These results have the potential to link the neonatal exposure to high doses of BPA in rats with the development of PCOS. Studies of doses and routes of administration more consistent with human exposures are needed to determine the relevance of these findings to human health. 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 Sprague-Dawley females. These results have the potential to link the neonatal exposure to high doses of BPA in rats with the development of PCOS. Studies of doses and routes of administration more consistent with human exposures are needed to determine the relevance of these findings to human health.