The effect of gestational diabetes on the expression of mitochondrial fusion proteins in placental tissue

Introduction: Gestational diabetes mellitus (GDM) poses a risk factor for fetal mortality and morbidity by directly affecting the placenta and fetus. Mitochondria are dynamic organelles that play a key role in energy production and conversion in placental tissue. Mitochondrial fusion and fission proteins are important in terms of providing mitochondrial dynamics, the adaptation of the cell to different conditions, and maintaining the metabolic stability of the cells. Although GDM shares many features with Type 2 diabetes mellitus (T2DM), different effects of these conditions on the mother and the child suggest that GDM may have specific pathological effects on placental cells. The aim of this study is to investigate the expression of mitochondrial dynamics, and mitochondrial protein folding markers in placentas from GDM patients and women with pre-existing diabetes mellitus.

Methods: Placentas were properly collected from women, who had pre-existing diabetes (Pre-DM), from women with gestational diabetes mellitus (GDM) and from healthy (non-diabetic) pregnant women. Levels of mitochondrial fusion markers were determined in these placentas by real time quantitative PCR and Western blot experiments.

Results: mRNA expressions and protein levels of mitochondrial fusion markers, mitofusin 1, mitofusin 2 (MFN1 and MFN2) and optical atrophy 1 (OPA1) proteins were found to be significantly lower in both Pre-DM placentas and those with GDM compared to healthy (non-diabetic) control group. Likewise, proteins involved in mitochondrial protein folding were also found to be significantly reduced compared to control group.

Discussion: Diabetes during pregnancy leads to processes that correlate with mitochondria dysfunction in placenta. Our results showed that mitochondrial fusion markers significantly decrease in placental tissue of women with GDM, compared to the healthy non-diabetic women. The decrease in mitochondrial fusion markers was more severe during GDM compared to the Pre-DM. Our results suggest that there may be differences in the pathophysiology of these conditions.