Neonatal exposure to bisphenol a and reproductive and endocrine alterations resembling the polycystic ovarian syndrome in adult rats.
Neonatal exposure to bisphenol a and reproductive and endocrine alterations resembling the polycystic ovarian syndrome in adult rats.
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DOI：
10.1289/ehp.0901257
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发表时间：
2010-09
影响因子：
10.4
通讯作者：
Libertun C
中科院分区：
文献类型：
--
作者：
Fernández M;Bourguignon N;Lux-Lantos V;Libertun C
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成分。几项研究报告了有效的体内效应，因为BPA作为雌激素激动剂和/或拮抗剂以及雄激素和甲状腺激素拮抗剂。我们研究了新生儿暴露于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（PND 1）至PND 10每天皮下注射500 μg/50 μL BPA蓖麻油[BPA 500;~ 10−4 M，剂量高于最低观察到的不良反应水平（LOAEL）50 mg/kg]、50 μg/50 μL（BPA 50）或5 μg/50 μL（BPA 50和BPA 5的剂量均低于LOAEL）或单独的蓖麻油载体。在成人中，我们研究了a）下丘脑外植体中促性腺激素释放激素（GnRH）的释放，B）血清性激素水平，以及c）卵巢形态、排卵和生育力。新生儿暴露于BPA与血清睾酮和雌二醇水平升高，成年期孕酮降低，体外GnRH分泌改变有关。暴露于BPA 500的动物卵巢形态发生改变，显示出大量囊肿。暴露于BPA 50的动物在发情的早晨生育能力降低，卵母细胞数量没有变化，而暴露于BPA 500的动物显示不育。在雌性Sprague-Dawley大鼠大脑性别分化期间暴露于高剂量BPA改变了下丘脑-垂体-性腺轴。这些结果有可能将新生大鼠暴露于高剂量BPA与多囊卵巢综合征的发展联系起来。需要对更符合人类接触情况的剂量和给药途径进行研究，以确定这些研究结果与人类健康的相关性。
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 μg/50 μL [BPA500; ~ 10−4 M, a dose higher than the lowest observed adverse effect level (LOAEL) of 50 mg/kg], 50 μg/50 μL (BPA50), or 5 μg/50 μL (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.
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在风险评估中，对鱼类生物标志物中内分泌干扰的筛查和测试是“路标”，而不是“交通信号灯”。
影响因子：
10.4
作者：
Hutchinson, Thomas H;Ankley, Gerald T;Segner, Helmut;Tyler, Charles R
通讯作者：
Tyler, Charles R
影响因子：
4.1
作者：
Rubin BS;Soto AM
通讯作者：
Soto AM
新生儿重症监护室早产儿接触双酚A和其他酚类物质。
影响因子：
10.4
作者：
Calafat, Antonia M.;Weuve, Jennifer;Ye, Xiaoyun;Jia, Lily T.;Hu, Howard;Ringer, Steven;Huttner, Ken;Hauser, Russ
通讯作者：
Hauser, Russ
影响因子：
2.9
作者：
Patisaul, HB;Fortino, AE;Polston, EK
通讯作者：
Polston, EK
影响因子：
3.6
作者：
Parborell, F;Irusta, G;Tesone, M
通讯作者：
Tesone, M