Department of Obstetrics and Gynecology, Nara Medical University, Kashihara, Japan.
Ms.Clinic MayOne, Kashihara, Japan.
Reprod Sci. 2022 Mar;29(3):653-667. doi: 10.1007/s43032-021-00505-6. Epub 2021 Mar 5.
The aim of this review is to summarize our current understanding of the molecular mechanism for the glucose metabolism, especially pyruvate dehydrogenase (PDH), during oocyte maturation, as well as future perspectives of therapeutic strategies for aging focusing on metabolic regulation between aerobic glycolysis and the tricarboxylic acid (TCA) cycle/oxidative phosphorylation (OXPHOS). Each keyword alone or in combination was used to search from PubMed. Glucose metabolism is a dynamic process involving "On" and "Off" switches by the pyruvate dehydrogenase kinase (PDK)-PDH axis, which is crucial for energy metabolism and mitochondrial efficiency in cumulus cell differentiation and oocyte maturation. Activation of PDK suppresses the conversion of pyruvate to acetyl-coenzyme A (acetyl-CoA) through the inactivation of PDH, which allows the cumulus cells to supply sufficient amounts of pyruvate, lactate, and nicotinamide adenine dinucleotide phosphate (NADPH) to the oocytes. On the other hand, inactivation of PDK in oocytes can produce adenosine triphosphate (ATP) through a metabolic shift from aerobic glycolysis to the TCA cycle/OXPHOS. The metabolic balance between aerobic glycolysis and TCA cycle/OXPHOS presents us with a number of enzymes, ligands, receptors, and antioxidants that are potential therapeutic targets, some of which have already been successfully pursued to improve fertility outcomes. However, there are also many reports that question their efficacy. In conclusion, understanding the molecular mechanisms involved in the PDK-PDH axis is a crucial step to advance in novel therapeutic strategies to improve oocyte quality.
本文旨在总结卵母细胞成熟过程中葡萄糖代谢（尤其是丙酮酸脱氢酶（PDH））的分子机制，以及未来针对代谢调节（有氧糖酵解与三羧酸循环/氧化磷酸化（TCA/OXPHOS）之间）的治疗策略的展望，聚焦于衰老。我们单独或组合使用每个关键字，从 PubMed 进行搜索。葡萄糖代谢是一个动态过程，涉及丙酮酸脱氢酶激酶（PDK）-PDH 轴的“开”和“关”，这对于卵丘细胞分化和卵母细胞成熟过程中的能量代谢和线粒体效率至关重要。PDK 的激活通过使 PDH 失活来抑制丙酮酸转化为乙酰辅酶 A（acetyl-CoA），从而允许卵丘细胞向卵母细胞提供足够量的丙酮酸、乳酸和烟酰胺腺嘌呤二核苷酸磷酸（NADPH）。另一方面，PDK 在卵母细胞中的失活可以通过从有氧糖酵解到 TCA/OXPHOS 的代谢转变来产生三磷酸腺苷（ATP）。有氧糖酵解与 TCA/OXPHOS 之间的代谢平衡为我们提供了许多酶、配体、受体和抗氧化剂，它们是潜在的治疗靶点，其中一些已经成功地用于改善生育结局。然而，也有许多报告质疑它们的疗效。总之，了解 PDK-PDH 轴涉及的分子机制是推进改善卵母细胞质量的新型治疗策略的关键步骤。
