Gene expression profiling of changes induced by maternal diabetes in the embryonic heart

• Temporal gene expression changes in the diabetes-exposed embryonic heart.
• Increased HIF-1α levels correspond to increased hypoxia in E10.5.
• Increased VEGF-A expression in E10.5 corresponds to increased HIF-1α.

Cardiovascular defects are one of the most common congenital defects associated with maternal diabetes. Based on whole embryo gene expression microarray analysis, 11 genes were chosen for temporal expression analysis of diabetes-exposed hearts. The majority of the selected genes were deregulated in diabetes-exposed hearts compared to our controls at E13.5, E14.5, and E18.5. We showed increased hypoxia and HIF-1α protein levels in diabetes-exposed hearts at E10.5, which is a critical time point for the induction of developmental defects associated with diabetic embryopathy. Additionally, we found increased cardiac Vegfa levels that might trigger developmental abnormalities associated with diabetic embryopathy. Our results show that maternal diabetes affects the temporal expression pattern of gene encoding molecules involved in heart development and tissue remodelling and that these molecules might affect heart maturation processes and thus, the final outcome of diabetic pregnancies.