Perinatal exposure to bisphenol-A alters peripubertal mammary gland development in mice
Perinatal exposure to bisphenol-A alters peripubertal mammary gland development in mice
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DOI：
10.1210/en.2005-0340
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发表时间：
2005-09-01
期刊：
影响因子：
4.8
通讯作者：
Soto, AM
中科院分区：
文献类型：
--
作者：
Muñoz-de-Toro, M;Markey, CM;Soto, AM
发育过程中暴露于雌激素类化学物质会导致与生殖相关的形态、功能和行为异常。人类暴露在双酚A(BPA)中，这是一种从牙科材料和塑料食品和饮料容器中渗出的雌激素化合物。本研究的目的是确定围产期暴露于与环境相关的低剂量双酚A[25和250 ng双酚A/公斤体重(BW)-d]对乳房青春期周围发育的影响。双酚A可增强去卵巢CD-1小鼠乳腺对雌二醇的敏感性。在30d龄的完好胎中，末端芽相对于腺管面积的面积和数量增加，而其凋亡活性降低。乳管长度与发情前期的首次年龄呈正相关；随着双酚A剂量的增加，这种相关性降低，这表明双酚A暴露减缓了乳管对间质的侵袭。黄体酮受体阳性的导管上皮细胞也显著增多，呈簇状分布，预示着未来的分支点。事实上，在4个月大的小鼠中，暴露于25 ng BPA/kg bw-d的小鼠的侧枝显著增强。总而言之，围产期暴露于环境相关剂量的双酚A会导致乳腺形态发生的持续性改变。特别令人关注的是青春期末端芽密度的增加以及以前在成年动物中报道的末端数量的增加，因为这两个结构是人类和啮齿动物癌症发生的部位。
Developmental exposure to estrogenic chemicals induces morphological, functional, and behavioral anomalies associated with reproduction. Humans are exposed to bisphenol-A (BPA), an estrogenic compound that leaches from dental materials and plastic food and beverage containers. The aim of the present study was to determine the effects of perinatal exposure to low, environmentally relevant doses of BPA [25 and 250 ng BPA/kg body weight (bw)-d] on the peripubertal development of the mammary gland. BPA exposure enhanced the mammary glands' sensitivity to estradiol in ovariectomized CD-1 mice. In their intact 30-d-old littermates, the area and numbers of terminal end buds relative to the gland ductal area increased whereas their apoptotic activity decreased. There was a positive correlation between ductal length and the age at first proestrus; that was reduced as the BPA dose increased, suggesting that BPA exposure slows down ductal invasion of the stroma. There was also a significant increase of progesterone receptor-positive ductal epithelial cells that were localized in clusters, suggesting future branching points. Indeed, lateral branching was significantly enhanced at 4 months of age in mice exposed to 25 ng BPA/kg bw-d. In conclusion, perinatal exposure to environmentally relevant BPA doses results in persistent alterations in mammary gland morphogenesis. Of special concern is the increased terminal end bud density at puberty as well as the increased number of terminal ends reported previously in adult animals, as these two structures are the sites at which cancer arises in humans and rodents.