Effects of phthalate esters on the developing reproductive tract of male rats
Effects of phthalate esters on the developing reproductive tract of male rats
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DOI：
10.1093/humupd/7.3.231
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发表时间：
2001-05-01
影响因子：
13.3
通讯作者：
Sar, M
中科院分区：
文献类型：
--
作者：
Foster, PMD;Mylchreest, E;Sar, M
邻苯二甲酸酯是一大类化学试剂，主要用作增塑剂和溶剂。此类化学物质的某些成员已被证明会导致生殖和发育毒性。最近的注意力集中在这些药物通过假定的抗雄激素机制干扰男性生殖发育的潜力上。观察集中于邻苯二甲酸二正丁酯 (DBP)、邻苯二甲酸二(2-乙基己基)酯 (DEHP) 和邻苯二甲酸丁基苄酯，大多数信息与 DBP 的剂量反应关系有关。在转录激活测定中，DBP、DEHP 或其主要代谢物均不与人类或啮齿动物雄激素受体 (AR) 相互作用。 DBP 在男性生殖系统发育的关键窗口期间施用，之后对产生的后代进行检查直至成年。 DBP 对发育中的男性生殖道产生显着影响，包括附睾和输精管畸形、尿道下裂、胸部乳头/乳晕保留和肛门生殖器距离缩短。令人惊讶的是，一些雄性后代在 100 日龄时就诱发了间质细胞腺瘤。所有这些事件都是在怀孕母鼠没有任何毒性的情况下发生的，对胎儿的睾丸进行了检查。大鼠在给予母鼠 DBP 后，睾酮水平显着降低，Leydig 细胞数量增加，Leydig 细胞 AR 和 3-β 羟基类固醇脱氢酶呈阳性。
Phthalate esters are a large group of chemical agents used predominantly as plasticizers and solvents. Certain members of this chemical class have been shown to cause reproductive and developmental toxicity. Recent attention has focused on the potential of these agents to interfere with male reproductive development through a postulated antiandrogenic mechanism. Observations have focused on di-n-butyl phthalate (DBP), di-(2-ethylhexyl) phthalate (DEHP) and butyl benzylphthalate, with most information relating to dose-response relationships obtained for DBP, Neither DBP, DEHP nor their major metabolites interacted with human or rodent androgen receptors (AR) in transcriptional activation assays. DBP was administered during the critical window of development of the male reproductive system, after which the resulting offspring were examined until adulthood. DBP elicited marked effects on the developing male reproductive tract, including malformations of the epididymis and vas deferens, and hypospadias, Retention of thoracic nipples/areolae and reductions in anogenital distance were also noted. Surprisingly, Leydig cell adenomas were induced in some male offspring at 100 days of age. All these events occurred in the absence of any toxicity in the pregnant dam, Examination of testes from fetal. rats indicated markedly reduced testosterone levels and increased Leydig cell numbers after DBP administration to the dams, Leydig cells were positive for AR and 3-betahydroxysteroid dehydrogenase.