Instituto de Biología y Medicina Experimental, Buenos Aires, Argentina.
Environ Health Perspect. 2010 Sep;118(9):1217-22. doi: 10.1289/ehp.0901257. Epub 2010 Apr 22.
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.
We investigated the effects of neonatal exposure to BPA on the reproductive axis in adult female Sprague-Dawley rats.
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.
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.
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.
双酚 A（BPA）是一种内分泌干扰物，是聚碳酸酯塑料、环氧树脂和聚苯乙烯的组成部分。多项研究报告称其具有强烈的体内作用，因为 BPA 表现为雌激素激动剂和/或拮抗剂，以及雄激素和甲状腺激素拮抗剂。
我们研究了新生期暴露于 BPA 对成年雌性 Sprague-Dawley 大鼠生殖轴的影响。
雌性大鼠从出生后第 1 天（PND1）至 PND10 每天经皮注射 BPA 于蓖麻油中，剂量分别为 500μg/50μL（BPA500；约 10-4M，该剂量高于 50mg/kg 的最低观察到不良效应水平（LOAEL），50μg/50μL（BPA50）或 5μg/50μL（BPA50 和 BPA5 均低于 LOAEL），或单独给予蓖麻油载体。在成年期，我们研究了 a）下丘脑组织培养物中促性腺激素释放激素（GnRH）的释放，b）血清性激素水平，和 c）卵巢形态、排卵和生育能力。
新生期暴露于 BPA 与血清睾酮和雌二醇水平升高、成年期孕激素水平降低以及体外 GnRH 分泌改变相关。暴露于 BPA500 的动物卵巢形态发生改变，表现为大量囊肿。暴露于 BPA50 的动物生育力降低，但发情早晨的卵母细胞数量无变化，而暴露于 BPA500 的动物则不育。
在大脑性分化期间暴露于高剂量 BPA 改变了雌性 Sprague-Dawley 大鼠的下丘脑-垂体-性腺轴。这些结果有可能将大鼠新生期暴露于高剂量 BPA 与多囊卵巢综合征的发生联系起来。需要研究更符合人类暴露剂量和途径的研究，以确定这些发现与人类健康的相关性。
