Molecular mechanisms in diabetic embryopathy

Diabetic embryopathy is one of many serious complications associated with diabetes. It is known that maternal diabetes increases the frequency of congenital defects up to ten times. The most common defects are cardiovascular and neural tube defects. Molecular mechanisms of diabetic embryopathy are still not known. This work contributes to elucidation of molecular processes leading to development of cardiovascular defects in diabetic embryopathy. This study is based on observation that maternal diabetes affects transcriptional regulation of hypoxia-inducible factor 1 (HIF-1) in developing embryo. To study the influence of maternal diabetes on HIF-1 signaling pathway, we used mouse model heterozygous for "knock-out" of Hif1α gene. Our analyses showed the negative combinational effects of maternal diabetes and Hif1α+/- genotype on embryonic development and increased risk of diabetic embryopathy. Histological analysis demonstrated the increased incidence of cardiovascular defects, particularly defects of interventricular septum and hypoplastic compact left ventricular wall in embryonic day (E) 14.5 Hif1α+/- embryos compared to wt littermates from the diabetic pregnancy. Using qPCR, we analyzed gene expression changes in the embryonic hearts at E9.5 and E10.5. We selected genes important for the..