Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, Missouri, United States of America.
PLoS One. 2010 Dec 28;5(12):e15901. doi: 10.1371/journal.pone.0015901.
Impaired oocyte quality has been demonstrated in diabetic mice; however, the potential pathways by which maternal diabetes exerts its effects on the oocyte are poorly understood. Cumulus cells are in direct contact with the oocyte via gap junctions and provide essential nutrients to support oocyte development. In this study, we investigated the effects of maternal diabetes on the mitochondrial status in cumulus cells. We found an increased frequency of fragmented mitochondria, a decreased transmembrane potential and an aggregated distribution of mitochondria in cumulus cells from diabetic mice. Furthermore, while mitochondrial biogenesis in cumulus cells was induced by maternal diabetes, their metabolic function was disrupted as evidenced by lower ATP and citrate levels. Moreover, we present evidence suggesting that the mitochondrial impairments induced by maternal diabetes, at least in part, lead to cumulus cell apoptosis through the release of cytochrome c. Together the deleterious effects on cumulus cells may disrupt trophic and signaling interactions with the oocyte, contributing to oocyte incompetence and thus poor pregnancy outcomes in diabetic females.
在糖尿病小鼠中已经证实卵母细胞质量受损；然而，母体糖尿病对卵母细胞产生影响的潜在途径尚不清楚。卵丘细胞通过缝隙连接与卵母细胞直接接触，并提供必需的营养物质来支持卵母细胞的发育。在这项研究中，我们研究了母体糖尿病对卵丘细胞中线粒体状态的影响。我们发现糖尿病小鼠的卵丘细胞中，线粒体碎片化的频率增加，跨膜电位降低，线粒体呈聚集分布。此外，尽管母体糖尿病诱导了卵丘细胞中线粒体的生物发生，但它们的代谢功能被破坏，表现为 ATP 和柠檬酸水平降低。此外，我们提供的证据表明，母体糖尿病引起的线粒体损伤至少部分通过细胞色素 c 的释放导致卵丘细胞凋亡。总之，这些对卵丘细胞的有害影响可能破坏与卵母细胞的营养和信号相互作用，导致卵母细胞功能不全，从而导致糖尿病女性的妊娠结局不佳。
