Loss of PDK1 Induces Meiotic Defects in Oocytes From Diabetic Mice

Frontiers in Cell and Developmental Biology

Qiang Wang¹  Feifei Hu²  Hongzheng Sun³  Longsen Han³  Na Zhang³  Juan Ge³  Shoubin Tang³  Xiaojing Hou⁴ 

[1] Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China;Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China;State Key Laboratory of Reproductive Medicine, Suzhou Municipal Hospital, Nanjing Medical University, Nanjing, China;Women’s Hospital of Nanjing Medical University, Nanjing Maternity and Child HealthCare Hospital, Nanjing, China;

关键词: oocyte;    meiosis;    diabetes;    spindle;    PDK1;   

DOI  :  10.3389/fcell.2021.793389

来源: DOAJ

【 摘 要 】

Maternal diabetes has been shown to impair oocyte quality; however, the underlying mechanisms remain unclear. Here, using a streptozotocin (STZ)-induced diabetic mouse model, we first detected and reduced expression of pyruvate dehydrogenase kinase 1 (PDK1) in diabetic oocytes, accompanying with the lowered phosphorylation of serine residue 232 on α subunit of the pyruvate dehydrogenase (PDH) complex (Ser232-PDHE1α). Importantly, forced expression of PDK1 not only elevated the phosphorylation level of Ser232-PDHE1α, but also partly prevented the spindle disorganization and chromosome misalignment in oocytes from diabetic mice, with no beneficial effects on metabolic dysfunction. Moreover, a phospho-mimetic S232D-PDHE1α mutant is also capable of ameliorating the maternal diabetes-associated meiotic defects. In sum, our data indicate that PDK1-controlled Ser232-PDHE1α phosphorylation pathway mediates the effects of diabetic environment on oocyte competence.

【 授权许可】

Unknown