Maternal diabetes increases the risk of caudal regression caused by retinoic acid
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摘要Maternal diabetes increases the risk of congenital malformations in the offspring of affected pregnancies. This increase arises from the teratogenic effect of the maternal diabetic milieu on the developing embryo, although the mechanism of this action is poorly understood. In the present study, we examined whether the vitamin A metabolite retinoic acid (RA), a common drug with well-known teratogenic properties, may interact with maternal diabetes to alter the incidence of congenital malformations in mice. Our results show that when treated with RA, embryos of diabetic mice are significantly more prone than embryos of nondiabetic mice to develop caudal regression, a defect that is highly associated with diabetic pregnancy in humans. By studying the vestigial tail (Wnt-3a(vt)) mutant, we provide evidence that Wnt-3a, a gene that controls the development of the caudal region, is directly involved in the pathogenic pathway of RA-induced caudal regression. We further show that the molecular basis of the increased susceptibility of embryos of diabetic mice to RA involves enhanced downregulation of Wnt-3a expression. This positive interaction between RA and maternal diabetes may have implications for humans in suggesting increased susceptibility to environmental teratogens during diabetic pregnancy.
著者Chan BWH, Chan KS, Koide T, Yeung SM, Leung MBW, Copp AJ, Loeken MR, Shiroishi T, Shum ASW
期刊名稱Diabetes
出版年份2002
月份9
日期1
卷號51
期次9
出版社AMER DIABETES ASSOC
頁次2811 - 2816
國際標準期刊號0012-1797
電子國際標準期刊號1939-327X
語言英式英語
Web of Science 學科類別Endocrinology & Metabolism; ENDOCRINOLOGY & METABOLISM

上次更新時間 2021-11-10 於 00:28