INSERM U965 UFR Médecine, Hôpital Lariboisière, Université Paris 7, F-75475 Paris, France.
Reprod Toxicol. 2011 Jul;32(1):15-25. doi: 10.1016/j.reprotox.2011.03.001. Epub 2011 Apr 23.
The impact of early exposure to endocrine disruptor mixtures on mammary gland development is poorly known. Here, we identify the effects of a conception to weaning exposure of rats to the phytoestrogen genistein (G) and/or the antiandrogen vinclozolin (V) at 1mg/kg-d, alone or in association. Using several approaches, we found that G- and GV-exposed rats displayed significantly greater epithelial branching and proliferation, wider terminal end buds than controls at PND35, as well as ductal hyperplasia and periductal fibrosis. Focal branching defects were present in V-exposed rats. An increased ER and AR expression was observed in G- and GV- as compared to V-exposed rats at PND35. Surprisingly, a significant number of GV- and to a lesser extent, V-exposed animals displayed abnormal hyperplasic alveolar structures at PND50. Thus, gestational and lactational exposure to low doses of genistein plus vinclozolin may seriously affect peripubertal development of the rat mammary gland.
早期暴露于内分泌干扰物混合物对乳腺发育的影响知之甚少。在这里，我们确定了在受孕至断奶期间，1mg/kg-d 的剂量下，单独或联合暴露于植物雌激素染料木黄酮（G）和/或抗雄激素伏氯唑（V）对大鼠的影响。通过多种方法，我们发现 G 组和 GV 组的大鼠在 PND35 时，上皮分支和增殖明显增加，末端芽宽度比对照组更大，并且导管增生和管周纤维化。V 组暴露的大鼠存在局灶性分支缺陷。与 V 组暴露的大鼠相比，G 组和 GV 组的 ER 和 AR 表达明显增加。令人惊讶的是，大量 GV 组，并且在较小程度上，V 组暴露的动物在 PND50 时表现出异常增生的肺泡结构。因此，妊娠期和哺乳期暴露于低剂量的染料木黄酮加伏氯唑可能会严重影响大鼠乳腺的青春期前发育。
