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Multi-Omics Reveal the Metabolic Changes in Cumulus Cells During Aging
Liangyue Shi1, Hengjie Wang2, Shuai Zhu2
1College of Animal Science & Technology, Nanjing Agricultural University, Nanjing, China.
Cell Proliferation
|March 5, 2025
Summary
Aging impairs oocyte quality due to molecular changes in cumulus cells. Supplementing serotonin (5-HT) improved aged oocytes, offering insights into fertility treatments for older females.
Area of Science:
- Reproductive biology
- Molecular mechanisms of aging
- Oocyte quality and development
Background:
- Maternal aging negatively impacts oocyte quality, but the underlying molecular mechanisms are not fully understood.
- Cumulus cells, crucial for oocyte development, communicate with oocytes via gap junctions.
- Understanding cumulus cell function in aging is key to addressing age-related fertility decline.
Purpose of the Study:
- To investigate the proteomic and metabolomic profiles of cumulus cells from young and aged mice.
- To identify molecular mechanisms contributing to age-related decline in oocyte competence.
- To explore potential therapeutic interventions for improving oocyte quality in aged females.
Main Methods:
- Proteomic and metabolomic profiling of cumulus cells from young and aged mice.
- Analysis of metabolic pathways, including fatty acid beta-oxidation, nucleotide metabolism, and tryptophan metabolism (serotonin synthesis and kynurenine catabolism).
- In vitro culture of cumulus-oocyte complexes (COCs) with serotonin (5-HT) supplementation to assess its effects on aged oocytes.
Main Results:
- Aged cumulus cells showed increased activity in fatty acid beta-oxidation and nucleotide metabolism, suggesting compensatory energy provision.
- Reduced kynurenine catabolism and a significant decrease in serotonin (5-HT) synthesis were observed in aged cumulus cells.
- Supplementation with 5-HT during COC culture ameliorated metabolic dysfunction and meiotic defects in oocytes from aged mice.
Conclusions:
- Comprehensive multi-omics data reveal age-related metabolic alterations in cumulus cells.
- Decreased serotonin (5-HT) synthesis in aged cumulus cells contributes to oocyte aging.
- Serotonin (5-HT) supplementation presents a potential strategy for improving oocyte quality and fertility in aged females.
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