ESPE Abstracts

Introduction: Gestational diabetes mellitus (GDM) is a common problem in pregnancy with metabolic consequences for the fetus and the postnatal period. The aim of this study was to investigate the effects of GDM on mitochondrial structure and function in cord blood mononuclear cells and placental tissue, and the relationship between clinical data and mitochondrial dynamics.

Method: In this prospective cohort study, singleton newborns without additional anomalies, above the 37 weeks' gestational age, born by cesarean section, born to mothers with GDM (GDM group, n = 12), and newborns with the same characteristics born to non-GDM mothers (control group, n = 12) were included. Clinical findings, cord blood pH, bicarbonate, lactate, and postnatal glucose monitoring were collected. Mitochondrial membrane potential (MMP), mitochondrial superoxide production (MitoSox), and mitochondrial mass measurements in cord blood mononuclear cells (CB-MNC) by flow cytometry using mitochondrial-specific fluorescent dyes were performed. MMP and MitoSox levels were also measured in the presence of the electron transport chain (ETC) complex inhibitors rotenone, oligomycin, and antimycin. Mitochondrial fusion (Mfn2) and fission (Drp1) protein levels were determined by Western blot analysis in placental tissues and CB-MNCs, and mtDNA copy number was examined in both placental tissues and CB-MNCs.

Results: The GDM and control groups were similar in terms of clinical findings (birth weight, postnatal adaptation, hypoglycaemia, polycythaemia). With regard to mitochondrial functions, it was shown that MMP and mitosox levels decreased in the GDM group. In the presence of rotenone, a complex I inhibitor, both MMP and MitoSox levels were significantly lower in the GDM group. MitoSox levels in the presence of antimycin (a complex III inhibitor) were found to be increased in the GDM group. MMP levels measured after incubation with FCCP (an uncoupling agent) followed by Mito Tracker Red were low in the GDM group. The MMP level measured after incubation with oligomycin followed by Mito Tracker Red increased more in the GDM group than in the control group.

Conclusion: It was observed that MMP and MitoSox levels were decreased in GDM group compared to the control group, indicating a low level of mitochondrial activity Measurements in the presence of specific inhibitors also indicate a defect in the ETC and thus in mitochondrial respiration and ATP synthesis. We have demonstrated differences in mitochondrial dynamics that may reflect disturbances in metabolic programming in neonates with GDM. These differences may be the 'footprints' of metabolic dysfunction in the future adult life.