Hyperglycemia and gestational diabetes suppress placental glycolysis and mitochondrial function and alter lipid processing

Abstract

The degree that maternal glycemia affects placental metabolism of trophoblast cell types [cytotrophoblast (CTB) and syncytiotrophoblast (SCT)] in pregnant persons with gestational diabetes mellitus (GDM) is unknown. We tested the hypotheses that (a) hyperglycemia suppresses the metabolic rates of CTB and SCT; and (b) low placental metabolic activity from GDM placentas is due to decreased oxygen consumption of CTB. Trophoblast cells isolated from GDM and non-GDM term placentas were cultured for 8-hour (CTB) and following syncytialization at 72-hour (SCT) in 5 mM of glucose or 25 mM of glucose. Oxygen consumption rates, glycolysis, ATP levels, and lipid droplet morphometries were determined in CTB and SCT. In CTB from GDM placentas compared to control CTB: (a) oxidative phosphorylation was decreased by 44% (41.8 vs 74.2 pmol O2/min/100 ng DNA, P =.002); (b) ATP content was 39% lower (1.1 × 10−7 vs 1.8 × 10−7 nM/ng DNA, P =.046); and (c) lipid droplets were two times larger (31.0 vs 14.4 µm2/cell, P