Maternal diabetes increases the risk of caudal regression caused by retinoic acid
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AbstractMaternal 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.
All Author(s) ListChan BWH, Chan KS, Koide T, Yeung SM, Leung MBW, Copp AJ, Loeken MR, Shiroishi T, Shum ASW
Journal nameDiabetes
Volume Number51
Issue Number9
Pages2811 - 2816
LanguagesEnglish-United Kingdom
Web of Science Subject CategoriesEndocrinology & Metabolism; ENDOCRINOLOGY & METABOLISM

Last updated on 2021-14-09 at 00:42