The dose-dependent dual effects of alpha-ketoglutarate (AKG) on cumulus oocyte complexes during in vitro maturation.

Publisher: BioMed Central Country of Publication: England NLM ID: 101170464 Publication Model: Electronic Cited Medium: Internet ISSN: 1478-811X (Electronic) Linking ISSN: 1478811X NLM ISO Abbreviation: Cell Commun Signal Subsets: MEDLINE

Original Publication: [London] : BioMed Central, c2003-

Ketoglutaric Acids*/pharmacology ; Ketoglutaric Acids*/metabolism ; Oocytes*/drug effects ; Oocytes*/metabolism ; Cumulus Cells*/drug effects ; Cumulus Cells*/metabolism ; Cumulus Cells*/cytology ; In Vitro Oocyte Maturation Techniques*/methods ; Reactive Oxygen Species*/metabolism; Animals ; Female ; Mice ; Dose-Response Relationship, Drug ; Mitochondria/metabolism ; Mitochondria/drug effects ; Growth Differentiation Factor 9/metabolism ; Growth Differentiation Factor 9/genetics ; Glutathione/metabolism ; Oxidative Stress/drug effects ; NADP/metabolism ; Apoptosis/drug effects ; Membrane Potential, Mitochondrial/drug effects

In this study, we reported for the first time the dose-dependent dual effects of Alpha-Ketoglutarate (AKG) on cumulus oocyte complexes (COCs) during in vitro maturation (IVM). AKG at appropriate concentration (30 µM) has beneficial effects on IVM. This includes improved cumulus expansion, oocyte quality, and embryo development. These effects are mediated through multiple underlying mechanisms. AKG reduced the excessive accumulation of reactive oxygen species (ROS) in cumulus cells, reduced the consumption of GSH and NADPH. Cumulus GSH and NADPH were transported to oocytes via gap junctions, thereby reducing the oxidative stress, apoptosis and maintaining the redox balance in oocytes. In addition, AKG improved the mitochondrial function by regulating the mitochondrial complex 1 related gene expression in oocytes to maintain mitochondrial membrane potential and ATP production. On the other hand, oocyte generated GDF9 could also be transported to cumulus cells to promote cumulus expansion. Conversely, a high concentration of AKG (750 µM) exerted adverse effects on IVM and suppressed the cumulus expansion as well as reduced the oocyte quality. The suppression of the cumulus expansion caused by high concentration of AKG could be rescued with GDF9 supplementation in COCs, indicating the critical role of GDF9 in IVM. The results provide valuable information on the variable effects of AKG at different concentrations on reproductive physiology.
(© 2024. The Author(s).)

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2023ZD04049 Agricultural Biological Breeding Major Project

Keywords: Alpha-ketoglutarate; Cumulus cells-oocyte communication; Cumulus oocyte complexes; In vitro maturation; Reactive oxygen species

0 (Ketoglutaric Acids)
0 (Reactive Oxygen Species)
0 (Growth Differentiation Factor 9)
GAN16C9B8O (Glutathione)
53-59-8 (NADP)

Date Created: 20241004 Date Completed: 20241004 Latest Revision: 20241006

20241006

PMC11448289

10.1186/s12964-024-01827-z

39363298