Glucose Metabolism in Mouse Cumulus Cells Prevents Oocyte Aging by Maintaining Both Energy Supply and the Intracellular Redox Potential
Glucose Metabolism in Mouse Cumulus Cells Prevents Oocyte Aging by Maintaining Both Energy Supply and the Intracellular Redox Potential
复制标题
小鼠卵丘细胞中的葡萄糖代谢通过维持能量供应和细胞内氧化还原电位来防止卵母细胞老化
DOI：
10.1095/biolreprod.110.089557
复制
发表时间：
2011-06-01
影响因子：
3.6
通讯作者：
Tan, Jing-He
中科院分区：
文献类型：
--
作者：
Li, Qing;Miao, De-Qiang;Tan, Jing-He
抑制卵母细胞排卵后老化对健康生殖和辅助生殖技术都很重要。一些研究表明，葡萄糖通过糖酵解促进卵母细胞减数分裂的恢复，但其他研究表明，它是通过戊糖磷酸途径（PPP）。此外，虽然发现丙酮酸可以防止卵母细胞老化，但其机制尚不清楚。本研究通过使用排卵后老化卵母细胞模型来解决这些问题。结果表明，虽然卵母细胞本身可以利用丙酮酸或乳酸来防止衰老，但除非有卵丘细胞存在，否则它不能利用葡萄糖。卵丘细胞的葡萄糖代谢通过糖酵解和PPP产生丙酮酸和NADPH来防止卵母细胞老化。而PPP的糖酵解抑制后，仍然发挥作用，糖酵解被完全灭活后，PPP的抑制。当PPP被完全抑制时，添加PPP的中间产物果糖-6-磷酸显著减轻卵母细胞的老化。乳酸通过其乳酸脱氢酶催化氧化为丙酮酸来防止卵母细胞老化，但丙酮酸通过其线粒体内代谢来抑制卵母细胞老化。然而，乳酸和丙酮酸都需要线粒体电子传递来防止卵母细胞老化。PPP和丙酮酸对卵母细胞衰老的抑制作用均涉及细胞内氧化还原状态的调节。总之，结果表明，卵丘细胞中的葡萄糖代谢通过维持能量供应和细胞内氧化还原电位来防止卵母细胞排卵后老化，并且）卵丘细胞中的糖酵解可能是有缺陷的，丙酮酸的产生取决于中间产物的PPP。
Inhibiting oocyte postovulatory aging is important both for healthy reproduction and for assisted reproduction techniques. Some studies suggest that glucose promotes oocyte meiotic resumption through glycolysis, but others indicate that it does so by means of the pentose phosphate pathway (PPP). Furthermore, although pyruvate was found to prevent oocyte aging, the mechanism is unclear. The present study addressed these issues by using the postovulatory aging oocyte model. The results showed that whereas the oocyte itself could utilize pyruvate or lactate to prevent aging, it could not use glucose unless in the presence of cumulus cells. Glucose metabolism in cumulus cells prevented oocyte aging by producing pyruvate and NADPH through glycolysis and PPP. Whereas PPP was still functioning after inhibition of glycolysis, the glycolysis was completely inactivated after inhibition of PPP. Addition of fructose-6-phosphate, an intermediate product from PPP, alleviated oocyte aging significantly when the PPP was totally inhibited. Lactate prevented oocyte aging through its lactate dehydrogenase-catalyzed oxidation to pyruvate, but pyruvate inhibited oocyte aging by its intramitochondrial metabolism. However, both lactate and pyruvate required mitochondrial electron transport to prevent oocyte aging. The inhibition of oocyte aging by both PPP and pyruvate involved regulation of the intracellular redox status. Together, the results suggest that glucose metabolism in cumulus cells prevented oocyte postovulatory aging by maintaining both energy supply and the intracellular redox potential and that) glycolysis in cumulus cells might be defective, with pyruvate production depending upon the PPP for intermediate products.