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

Amy M. Valent, Haeri Choi, Kevin S. Kolahi, Kent L. Thornburg

Research output: Contribution to journalArticlepeer-review

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 <.001) and 1.7 times more numerous (13.5 vs 7.9 lipid droplets/cell, P <.001). Hyperglycemia suppressed CTB glycolysis by 55%-60% (mean difference 20.4 [GDM, P =.008] and 15.4 [non-GDM, P =.029] mpH/min/100 ng DNA). GDM SCT was not metabolically different from non-GDM SCT. However, GDM SCT had significantly decreased expression of genes associated with differentiation including hCG, GCM1, and syncytin-1. We conclude that suppressed metabolic activity by the GDM placenta is attributable to metabolic dysfunction of CTB, not SCT. Critical placental hormone expression and secretion are decreased in GDM trophoblasts.

Original languageEnglish (US)
Article numbere21423
JournalFASEB Journal
Volume35
Issue number3
DOIs
StatePublished - Mar 2021

Keywords

  • BODIPY
  • cytotrophoblast
  • gestational diabetes
  • hyperglycemia
  • lipids
  • metabolism
  • mitochondria
  • mitochondrial respiration
  • placenta
  • syncytiotrophoblast

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Fingerprint Dive into the research topics of 'Hyperglycemia and gestational diabetes suppress placental glycolysis and mitochondrial function and alter lipid processing'. Together they form a unique fingerprint.

Cite this