EP02.02: Placental involvement in gestational diabetes pathophysiology may link to maternal circulating antioxidant capacity and microRNA expression

Gestational diabetes (GDM) may be controlled with diet, but requires medication if severe; however, what leads to severe GDM in some women is unclear. We aimed to determine if the placental stress-response is altered in GDM compared to healthy pregnancies and is distinct between mild (diet) and severe (medicated) GDM pregnancies. Besides, we profiled maternal circulating antioxidant capacity and microRNA expression. Placental tissue (≥37 week's gestation) and maternal plasma (26–28 week's gestation) were collected from control (uncomplicated), GDM diet (GDMD), and GDM medicated (GDMM) pregnancies (n≥8 per group). Groups were matched for delivery mode, maternal age, maternal BMI, and infant weight. Placental expression of 239 genes was measured by qPCR. Antioxidant capacity was measured by activity assay. Maternal circulating expression of 800 microRNAs was measured using the nCounter system. Twenty placental genes had potentially biologically meaningful changes, eight genes down-regulated and four genes up-regulated in GDM compared to control. Eight genes were up-regulated in GDMD but down-regulated in GDMM. Placental antioxidant capacity was decreased in male GDMD and female GDMM, and increased in female GDMD, relative to controls. Circulating antioxidant capacity was reduced in GDMM compared to GDMD and controls. Circulating expression of 16 microRNAs was different between GDM and controls. Nine microRNAs were upregulated in GDMD, and five in GDMM, compared to controls. The placenta may not be adapting successfully in severe GDM, with lower expression of genes involved in antioxidants, metabolism, and drug processing in GDMM placentae, suggesting a dampened response to stimuli. This gene level response may relate to lowered antioxidant capacity in GDM in both placental and maternal compartments. Circulating antioxidant capacity and microRNA profiles may be effective in distinguishing which women are likely to require medication.