ArticleCell death & disease2022
Enhanced glycolysis in granulosa cells promotes the activation of primordial follicles through mTOR signaling.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed, 136 citations in OpenAlex.
- Integrative dual-track transcriptomics reveals stage-specific coordination, regulatory divergence, and HSP90AA1-associated remodeling in human folliculogenesis.Journal, genetic engineering & biotechnology · 2026Article
- Restoring glucose metabolic homeostasis to attenuate ovarian aging: mechanisms and clinical prospects.Journal of ovarian research · 2026Review
- Icaritin improves pregnancy outcomes in endometriosis by inhibiting ovarian granulosa cell senescence.Molecular biology reports · 2026Article
- Integrated Multi-Omics Reveals Gut Microbiota-Ovarian Crosstalk of Laying Performance Between High- and Low-Laying Muscovy Ducks.Veterinary sciences · 2026Article
- The role of mTOR signaling in regulating the quality of mammalian oocytes.Journal of assisted reproduction and genetics · 2026Review
- Rapamycin co-exposure fails to reduce cisplatin-induced damage in GC6-spg spermatogonial cell line.Reproduction & fertility · 2026Article
- Calcitriol is involved in maintaining primordial follicle reserve through the inhibition of the PI3K/Akt signaling pathway.Journal of ovarian research · 2026Article
- Ovarian aging: maintenance and activation of the primordial follicle pool.Journal of ovarian research · 2026Review
- Epigenetic deciphering of ovarian aging: multilayer interactive mechanisms and targeted reversal strategies.Epigenetics & chromatin · 2026Review
- Dysregulated post‑translational modifications in granulosa cells drive ovarian dysfunction and potential infertility applications (Review).International journal of molecular medicine · 2026Review
- Review
- ReducediScience · 2026Article
- A Follicle Size Window of Competence for In Vitro Embryo Production in High-Producing Dairy Cows: Evidence from OPU-IVP Performance and Follicular Fluid Profiling.Animals : an open access journal from MDPI · 2026Article
- Retinoic Acid and Calcitriol Protect Mouse Primordial Follicles from Cyclophosphamide Treatment-Induced Apoptosis.Antioxidants (Basel, Switzerland) · 2026Article
- The role of metabolic reprogramming in oocyte development: research progress and prospects.Frontiers in reproductive health · 2026Review
- Follicular fluid from women with polycystic ovary syndrome induces granulosa cells metabolic dysfunction that is exacerbated by obesity.Frontiers in endocrinology · 2026Article
- Preventing ovarian aging: from redox-targeted strategies to extracellular vesicle-based therapies.Frontiers in aging · 2026Review
- The mechanisms of energy balance between oxidative phosphorylation and glycolysis in human ovarian granulosa cells.Frontiers in physiology · 2026Article
- The Role of Anethole in Reproductive Physiology and In Vitro Biotechnologies-A Review.Reproduction in domestic animals = Zuchthygiene · 2026Review
- Living in a chemical cocktail: real-world mixture exposures and their impact on ovarian function.The Journal of reproduction and development · 2026Review
19 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In mammals, nonrenewable primordial follicles are activated in an orderly manner to maintain the longevity of reproductive life. Mammalian target of rapamycin (mTOR)-KIT ligand (KITL) signaling in pre-granulosa cells and phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt)-forkhead Box O3a (FOXO3a) signaling in oocytes are important for primordial follicle activation. The activation process is accompanied by the enhancement of energy metabolism, but the causal relationship is unclear. In the present study, the levels of glycolysis-related proteins GLUT4, HK1, PFKL, and PKM2 were significantly increased in granulosa cells but were decreased in oocytes during the mouse primordial-to-primary follicle transition. Both short-term pyruvate deprivation in vitro and acute fasting in vivo increased the glycolysis-related gene and protein levels, decreased AMPK activity, and increased mTOR activity in mouse ovaries. The downstream pathways Akt and FOXO3a were phosphorylated, resulting in mouse primordial follicle activation. The blockade of glycolysis by 2-deoxyglucose (2-DG), but not the blockade of the communication network between pre-granulosa cells and oocyte by KIT inhibitor ISCK03, decreased short-term pyruvate deprivation-promoted mTOR activity. Glycolysis was also increased in human granulosa cells during the primordial-to-primary follicle transition, and short-term pyruvate deprivation promoted the activation of human primordial follicles by increasing the glycolysis-related protein levels and mTOR activity in ovarian tissues. Taken together, the enhanced glycolysis in granulosa cells promotes the activation of primordial follicles through mTOR signaling. These findings provide new insight into the relationship between glycolytic disorders and POI/PCOS.
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