Exposure to environmentally relevant doses of the xenoestrogen bisphenol-A alters development of the fetal mouse mammary gland
Exposure to environmentally relevant doses of the xenoestrogen bisphenol-A alters development of the fetal mouse mammary gland
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DOI：
10.1210/en.2006-0561
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发表时间：
2007-01-01
期刊：
影响因子：
4.8
通讯作者：
Soto, Ana M.
中科院分区：
文献类型：
--
作者：
Vandenberg, Laura N.;Maffini, Maricel V.;Soto, Ana M.
人类经常接触双酚 A (BPA)，这是一种从牙科材料、食品和饮料容器以及其他塑料消费品中浸出的雌激素化合物。围产期 BPA 暴露对小鼠乳腺的影响在青春期和成年期（暴露期结束后很长一段时间）都已观察到。本研究的目的是检查胚胎第 18 天 (E) 的胎儿乳腺发育，并评估暴露于环境相关剂量的 BPA 后组织组织和组织结构的变化。在未暴露的胎儿中，胎儿在子宫中相对于其雌性和雄性兄弟姐妹的相对位置影响了导管树的生长，导管树在放置在两个雄性之间的雌性中比放置在两个雌性之间的雌性中更为发育。从 E8 到 E18，每天将母鼠暴露于每公斤体重 250 ng BPA 的环境中，暴露胎儿的导管面积和导管延伸显着增加，并消除了位置差异。在基质中，BPA 暴露促进了脂肪垫的成熟并改变了胶原蛋白的定位。在上皮内，接触 BPA 会导致细胞尺寸减小并延迟管腔形成。由于乳腺发育依赖于这些区室之间的相互作用，因此脂肪垫的提前成熟和细胞外基质的变化可能是上皮中观察到的生长、细胞大小和管腔形成改变的原因。这些结果表明，在围产期暴露的小鼠中在青春期和成年期观察到的乳腺表型的改变起源于胎儿发育。
Humans are routinely exposed to bisphenol-A ( BPA), an estrogenic compound that leaches from dental materials, food and beverage containers, and other plastic consumer products. Effects of perinatal BPA exposure on the mouse mammary gland have been observed in puberty and adulthood, long after the period of exposure has ended. The aim of this study was to examine fetal mammary gland development at embryonic day ( E) 18 and assess changes in the tissue organization and histoarchitecture after exposure to an environmentally relevant dose of BPA. In unexposed fetuses, the relative position of the fetus with respect to its female and male siblings in the uterus influenced growth of the ductal tree, which was more developed in females placed between two males than in females placed between two females. Exposure of dams to 250 ng BPA per kilogram body weight per day from E8 to E18 significantly increased ductal area and ductal extension in exposed fetuses and obliterated positional differences. In the stroma, BPA exposure promoted maturation of the fat pad and altered the localization of collagen. Within the epithelium, BPA exposure led to a decrease in cell size and delayed lumen formation. Because mammary gland development is dependent on reciprocal interactions between these compartments, the advanced maturation of the fat pad and changes in the extracellular matrix may be responsible for the altered growth, cell size, and lumen formation observed in the epithelium. These results suggest that alterations in mammary gland phenotypes observed at puberty and adulthood in perinatally exposed mice have their origins in fetal development.