Department of Medical Biology, Faculty of Medicine, Aydın Adnan Menderes University, AYDIN, Turkey.
Department of Reproductive Medicine and Infertility, Hisar Intercontinental Hospital, ISTANBUL, Turkey.
Placenta. 2021 Nov;115:106-114. doi: 10.1016/j.placenta.2021.09.015. Epub 2021 Sep 24.
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.
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.
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.
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.
妊娠糖尿病（GDM）通过直接影响胎盘和胎儿，对胎儿死亡率和发病率构成风险因素。线粒体是动态细胞器，在胎盘组织的能量产生和转化中起着关键作用。线粒体融合和裂变蛋白对于提供线粒体动力学、细胞适应不同条件以及维持细胞代谢稳定性非常重要。尽管 GDM 与 2 型糖尿病（T2DM）有许多共同特征，但这些情况对母亲和孩子的不同影响表明，GDM 可能对胎盘细胞有特定的病理影响。本研究旨在研究线粒体动力学和线粒体蛋白折叠标志物在 GDM 患者和患有预先存在的糖尿病的妇女的胎盘组织中的表达。
从患有预先存在的糖尿病（Pre-DM）的妇女、患有妊娠糖尿病（GDM）的妇女和健康（非糖尿病）孕妇中适当收集胎盘。通过实时定量 PCR 和 Western blot 实验确定这些胎盘中线粒体融合标志物的水平。
线粒体融合标志物的 mRNA 表达和蛋白水平，包括线粒体融合蛋白 1、线粒体融合蛋白 2（MFN1 和 MFN2）和光学萎缩蛋白 1（OPA1）蛋白，在 Pre-DM 胎盘和 GDM 胎盘与健康（非糖尿病）对照组相比均显着降低。同样，与对照组相比，参与线粒体蛋白折叠的蛋白质也显着减少。
怀孕期间的糖尿病会导致与胎盘功能障碍相关的过程。我们的结果表明，与健康非糖尿病妇女相比，GDM 妇女的胎盘组织中线粒体融合标志物显着减少。与 Pre-DM 相比，GDM 中线粒体融合标志物的减少更为严重。我们的结果表明，这些情况的病理生理学可能存在差异。
