Dietary bisphenol A prevents ovarian degeneration and bone loss in female mice lacking the aromatase gene (Cyp19 ).
Dietary bisphenol A prevents ovarian degeneration and bone loss in female mice lacking the aromatase gene (Cyp19 ).
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DOI：
10.1046/j.1432-1033.2002.02879.x
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发表时间：
2002-04
期刊：
影响因子：
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通讯作者：
K. Toda;C. Miyaura;Teruhiko Okada;Y. Shizuta
中科院分区：
文献类型：
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作者：
K. Toda;C. Miyaura;Teruhiko Okada;Y. Shizuta
我们之前通过靶向破坏 Cyp19 产生缺乏芳香酶活性的小鼠（ArKO 小鼠），并报告了雌性小鼠的表型，显示卵巢中出血形成和卵泡耗竭、子宫尺寸缩小和骨质流失。在本研究中，我们研究了膳食双酚 A (BPA)（一种用于生产聚碳酸酯的单体，已知具有雌激素活性）对 ArKO 小鼠这些表型的影响。当 ArKO 小鼠喂食补充有 0.1% 或 1% (w/w) BPA 的食物 5 个月时，它们以剂量依赖的方式免受卵巢退化、子宫缩小和骨质流失的影响。 ArKO小鼠卵巢RNA的Northern印迹分析显示，与野生型小鼠卵巢相比，胰岛素样生长因子(IGF)-I、IGF-I受体、生长分化因子9和骨形态发生蛋白15的表达水平存在差异。饮食 BPA 可以恢复表达水平的差异。在 ArKO 子宫中，黄体酮受体和血管内皮生长因子 mRNA 的表达减少，并通过 BPA 恢复到野生型小鼠的水平。相比之下，BPA对野生型小鼠的卵巢、子宫和骨骼结构几乎没有影响。总之，BPA 对成年雌性 ArKO 小鼠的生殖道和骨骼组织具有明显的雌激素作用。这些结果表明 ArKO 小鼠是适合研究雌激素化学物质以及雌激素体内作用的动物模型。
We previously generated mice lacking aromatase activity by targeted disruption of Cyp19 (ArKO mice), and reported phenotypes of the female mice, showing hemorrhage formation and follicular depletion in the ovary, diminution in uterine size, and bone loss. In the present study, we examined the influence of dietary bisphenol A (BPA), a monomer used for the production of polycarbonate and known to have estrogenic activity, on these phenotypes of the ArKO mice. When ArKO mice were fed chow diets supplemented with 0.1% or 1% (w/w) BPA for 5 months, they were protected from ovarian degeneration, uterine diminution and bone loss in a dose-dependent manner. Northern blot analyses of ovarian RNA of ArKO mice showed differences in the expression levels of insulin-like growth factor (IGF)-I, IGF-I receptor, growth differentiation factor 9 and bone morphogenetic protein 15 as compared with those in the ovaries of wild-type mice. The differences in the expression levels were restored by dietary BPA. In the ArKO uteri, expression of progesterone receptor and vascular endothelial growth factor mRNAs was diminished, and was restored by BPA to the levels in wild-type mice. In contrast, BPA had little effect on the ovarian, uterine and skeletal structures of wild-type mice. In conclusion, estrogenic effects of BPA on the reproductive tract as well as skeletal tissue were evident in adult female ArKO mice. These results suggest that the ArKO mouse is an animal model suitable for studying effects of estrogenic chemicals as well as estrogen in vivo.