Estrogen-like disruptive effects of dietary exposure to bisphenol A or 17α-ethinyl estradiol in CD1 mice.
Estrogen-like disruptive effects of dietary exposure to bisphenol A or 17α-ethinyl estradiol in CD1 mice.
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DOI：
10.1177/1091581812463254
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发表时间：
2012-11
影响因子：
2.2
通讯作者：
Belcher SM
中科院分区：
文献类型：
--
作者：
Kendig EL;Buesing DR;Christie SM;Cookman CJ;Gear RB;Hugo ER;Kasper SN;Kendziorski JA;Ungi KR;Williams K;Belcher SM
双酚A(BPA)是一种内分泌干扰物，在野外和建筑环境中普遍存在。由于研究设计的变异性，双酚A的破坏性作用已被证明很难在实验上复制。这项研究旨在评估饮食中双酚A暴露的破坏性作用，同时仔细控制已知的混杂因素。将亲本CD1小鼠习服于含有双酚A(0.03ppm、0.3ppm、3ppm、30ppm或300ppm)或17α-乙烯基雌二醇(EE0.03ppm、0.001 ppm和0.01ppm)的限定饲料中，并培育出后代(F1)，在与父母相同的饲料中维持整个成年期。在F1女性中，所有EE和30ppm双酚A暴露组的子宫重量都增加了，这表明了双酚A的模型敏感性和雌激素样作用。在接触双酚A的女性中，没有观察到与治疗相关的父母生殖功能，或者女性后代的青春期和代谢功能的时间差异。在F1男性中，观察到体重、肥胖和葡萄糖耐量的轻微变化，这与代谢功能的改善是一致的。随着催乳素的增加和循环睾酮水平的增加，雄性仔猪出生后第21天的肛门距离分别增加了0.03和3.0ppm BPA，肛门-生殖器距离增加了0.03ppm BPA。暴露在3.0ppm双酚A环境中的精子数量也有所增加。总体而言，BPA被发现对各种终点有适度的、性别特异性的内分泌干扰作用，低于已确定的未观察到不良反应的水平。许多效应的剂量反应特征是非单调的，不能通过高剂量外推来预测。
Bisphenol A (BPA) is an endocrine disrupting chemical that is ubiquitous in wild and built environments. Due to variability in study design, the disruptive effects of BPA have proven difficult to experimentally replicate. This study was designed to assess the disruptive actions of dietary BPA exposure, while carefully controlling for known confounders. Parental CD1 mice were acclimated to defined diet containing BPA (0.03, 0.3, 3, 30, or 300 ppm) or 17α-ethinyl estradiol (EE; 0.0001, 0.001, and 0.01 ppm) and bred to produce progeny (F1) that were maintained through adulthood on the same diet as the parents. In F1 females, uterine weights were increased in all EE and the 30-ppm BPA-exposure groups, demonstrating model sensitivity and estrogen-like actions of BPA. In BPA-exposed females, no treatment-related differences were observed in parental reproductive function, or in the timing of puberty and metabolic function in female offspring. In F1 males, modest changes in body weight, adiposity and glucose tolerance, consistent with improved metabolic function, were observed. Associated with increased prolactin and increased circulating testosterone levels, balanopreputial separation was accelerated by 0.03 and 3.0 ppm BPA and anogenital distance at postnatal day 21 was increased in males by 0.03 ppm BPA. Sperm counts were also increased with 3.0 ppm BPA exposures. Overall, BPA was found to have modest, sex specific endocrine disruptive effects on a variety of end points below the established no observed adverse effect level. The dose response characteristics for many of the effects were nonmonotonic and not predictable from high-dose extrapolations.