To identify microRNAs (miRNAs) whose expression levels in fetal tissues are altered by exposure to a diabetic milieu and elucidate the impact on target protein expression. Gestational diabetes mellitus (GDM) impacts both immediate and future disease risk in the offspring. We hypothesized that GDM alters miRNA expression in human umbilical vein endothelial cells (HUVECs) that may influence metabolic processes.A cross-sectional design compared differences in miRNA expression in HUVECs and target protein abundance in placentae between infants of women with GDM (IGDM) and infants born to normoglycemic controls. miRNAs were identified using microarray profiling and literature review and validated by qPCR. In vitro transfection studies explored the impact of the miRNA on target protein expression. Expression of seven miRNA species, miR-30c-5p, 452-5p, 126-3p, 130b-3p, 148a-3p, let-7a-5p, and let-7g-5p, was higher in the HUVECs of IGDM. Abundance of the catalytic subunit of AMP-activated protein kinase (AMPKα1) was decreased in the HUVECs and BeWo cells (transformed trophoblast cell line) transfected with miR-130b and miR-148a mimics. AMPKα1 expression was also decreased in placental tissues of IGDM.The expression of several miRNAs were altered by in utero exposure to DM in infants of women whose dysglycemia was very well-controlled by current standards. Decreased expression of AMPKα1 as a result of increased levels of miR-130b and miR-148a may potentially explain the decrease in fat oxidation we reported in infants at one month of age and, if persistent, may predispose offspring to future metabolic disease.
- gestational diabetes
- fetal programming
- ©2016 The Author(s)
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