Mitochondrial function and glucose metabolism in the placenta with gestational diabetes mellitus: Role of miR-143

A predisposing factor for development of the hyperglycemic state of gestational diabetes mellitus (GDM) is obesity. We previously showed that increasing maternal obesity is associated with significant reductions in placental mitochondrial respiration. MicroRNA (miR)-143 has been previously shown to regulate the metabolic switch from oxidative phosphorylation to aerobic glycolysis in cancer tissues. We hypothesized that mitochondrial respiration is reduced and aerobic glycolysis is upregulated via changes in miR-143 expression in the placenta of women with GDM. Placental tissue was collected at term from women with A1GDM (controlled by diet), A2GDM (controlled by medication), and BMI-matched controls (CTRL). miR-143 expression was measured by RT-PCR. Expression of mitochondrial complexes, transcription factors PGC1α and PPARγ, components of mTOR signaling, glucose transporter Glut1 and glycolytic enzymes (HK-2, PFK, and LDH) were measured by Western Blot. Trophoblast respiration was measured by XF24 Analyzer. Expression of miR-143, mitochondrial complexes, and PPARγ and PGC1α, which act downstream of miR-143, were significantly decreased in A2GDM placentae vs. A1GDM and CTRL (p