Table1_Loss of PDK1 Induces Meiotic Defects in Oocytes From Diabetic Mice.DOCX (21.18 kB)
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Table1_Loss of PDK1 Induces Meiotic Defects in Oocytes From Diabetic Mice.DOCX

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posted on 20.12.2021, 04:29 by Juan Ge, Na Zhang, Shoubin Tang, Feifei Hu, Xiaojing Hou, Hongzheng Sun, Longsen Han, Qiang Wang

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.

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