tailieunhanh - Báo cáo Y học: Dietary bisphenol A prevents ovarian degeneration and bone loss in female mice lacking the aromatase gene (Cyp19 )

Department of Medical Chemistry, Kochi Medical School, Nankoku, Japan; 2Department of Biochemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Science, Japan; 3Department of Anatomy and Cell Biology, Kochi Medical School, Nankoku, Japan 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. | Eur. J. Biochem. 269 2214-2222 2002 FEBS 2002 doi Dietary bisphenol A prevents ovarian degeneration and bone loss in female mice lacking the aromatase gene Cyp19 Katsumi Toda1 Chisato Miyaura2 Teruhiko Okada3 and Yutaka Shizuta1 1 Department of Medical Chemistry Kochi Medical School Nankoku Japan department of Biochemistry School of Pharmacy Tokyo University of Pharmacy and Life Science Japan 3 Department of Anatomy and Cell Biology Kochi Medical School Nankoku Japan 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 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 mor phogenetic 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 .

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