Glucose Metabolism in Mouse Cumulus Cells Prevents Oocyte Aging by Maintaining Both Energy Supply and the Intracellular Redox Potential1

Abstract

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.

Female Aging Alters Expression of Human Cumulus Cells Genes that Are Essential for Oocyte Quality

“…These results are consistent with the observations reported recently [17, 19]. Indeed, the energy supplied by the CCs is known to be required for oocyte quality [44, 45]. Some members of the TGF - β superfamily, which are crucial to processes that govern follicle development and oocyte maturation [46], were underexpressed in the CC older group such as AMH (Anti-Mullerien Hormone), TGFB1 , inhibin ( INHA ),and activin receptor ( ACVR2B ).…”

Oocyte aging-induced Neuronatin (NNAT) hypermethylation affects oocyte quality by impairing glucose transport in porcine

“…However, low temperature and antioxidants could overcome the deleterious effects induced by OS3233. As proved that pyruvate involved mitochondrial electron transport and MCTs and regulated both the intracellular redox status and energy supply to inhibit oocyte aging9. Our data showed that the decrease of NNAT activity impaired partial transported glucose, which may affect the production of antioxidants, like pyruvate.…”

“…Glucose metabolism affected both oocyte maturation and following development of oocytes after fertilization and oocyte aging89. Glucose metabolism in cumulus cells prevented oocyte aging by producing pyruvate and NADPH through glycolysis and pentose phosphate pathway (PPP).…”

“…Both pyruvate and lactate involved mitochondrial electron transport and monocarboxylate transporters (MCTs) were active on the plasma membrane and/or mitochondria of the aging oocyte. Pyruvate regulated both the intracellular redox status and energy supply at a higher concentration but regulated only energy supply at a lower concentration to inhibit oocyte aging9. Well-balanced and timed glucose metabolism need enough and timely glucose transport in oocytes10.…”

Towards Functional Annotation of the Preimplantation Transcriptome: An RNAi Screen in Mammalian Embryos

“…In summary, GO term analysis offered no striking outliers in functional categories within our screen results and suggests that preimplantation development equally requires all aspects of cellular and molecular function for success. Supporting this notion, previous studies have found essential roles during preimplantation for genes within each of these functional categories (including DNA/RNA/protein binding4546, catalytic activity4748, various transporter activity495051). …”