Maternal Diabetes Alters microRNA Expression in Fetal Exosomes, Human Umbilical Vein Endothelial Cells and Placenta

BACKGROUND: Exposure to diabetes in utero influences future metabolic health of the offspring. MicroRNAs (miRNA) are small non-coding RNAs that may contribute mechanistically to the effects on offspring imparted by diabetes mellitus (DM) during pregnancy. We hypothesized that exposure to DM during pregnancy influences select miRNAs in fetal circulation, in human umbilical vein endothelial cells (HUVEC), and placenta. METHODS: miRNA abundance was quantified using real-time PCR from RNA isolated from umbilical cord serum exosomes, HUVEC and placenta exposed to diabetes or normoglycemia during pregnancy. The abundance of each of these miRNAs was determined by comparison to a known standard and the relative expression assessed using the 2(−ΔΔCt) method. Multivariable regression models examined the associations between exposure to diabetes during pregnancy and miRNA expression. RESULTS: miR-126–3p was highly abundant in fetal circulation, HUVEC and placenta. Diabetes exposure during pregnancy resulted in lower expression of miR-148a-3p and miR-29a-3p in the HUVEC. In the placenta, for miR-126–3p, there was a differential effect of DM by birthweight between DM versus control group, expression being lower at the lower birth weight, however not different at the higher birthweight. CONCLUSION: Exposure to DM during pregnancy alters miRNA expression in the offspring in a tissue specific manner.