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

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

  • Cell Commun Signal. 2024 Oct 3;22(1):472. doi: 10.1186/s12964-024-01827-z.
Yunjie Liu 1,  Xin Xiao 1,  Likai Wang 1,  Yao Fu 1,  Songyang Yao 1,  Xuening Liu 1,  Boda Chen 1,  Jiarui Gao 1,  Yaying Zhai 1,  Zixia Shen 1,  Laiqing Yan 1,  Yiwei Wang 1,  Pengyun Ji 1,  Bingyuan Wang 1,  Guoshi Liu 2
Affiliations

Affiliations

  • 1 State Key Laboratory of Animal Biotech Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agricultural, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, No. 2 Yuanmingyuan West road, Beijing, 100193, China.
  • 2 State Key Laboratory of Animal Biotech Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agricultural, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, No. 2 Yuanmingyuan West road, Beijing, 100193, China. gshliu@cau.edu.cn.
PMID: 39363298 DOI: 10.1186/s12964-024-01827-z
Abstract

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.

Keywords

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

Figures
Products