title: Mitochondrial dysfunction and apoptosis in cumulus cells of type I diabetic mice.
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.forename: Antonina I
authors.initials: AI
authors.lastname: Frolova
authors.forename: Scott
authors.initials: S
authors.lastname: Purcell
authors.forename: Katie
authors.initials: K
authors.lastname: Adastra
authors.forename: Erica
authors.initials: E
authors.lastname: Schoeller
authors.forename: Maggie M
authors.initials: MM
authors.lastname: Chi
authors.forename: Tim
authors.initials: T
authors.lastname: Schedl
authors.forename: Kelle H
authors.initials: KH
authors.lastname: Moley
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D019343:Citric Acid / Q000737:chemistry; D054885:Cumulus Cells / Q000166:cytology*; D003921:Diabetes Mellitus, Experimental / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D020287:In Situ Nick-End Labeling; D051379:Mice; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000378:metabolism*; D009865:Oocytes / Q000166:cytology*; D017382:Reactive Oxygen Species; D015398:Signal Transduction
chemical_list: D017382:Reactive Oxygen Species; D019343:Citric Acid; D000255:Adenosine Triphosphate