ArticleNature aging2023
Granulosa cell mevalonate pathway abnormalities contribute to oocyte meiotic defects and aneuploidy.
Article in Nature aging, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 39 citations in OpenAlex.
- Maternal age as a driver of genome instability: mechanisms linking aneuploidy, mutagenesis and mitochondrial dysfunction.Archives of toxicology · 2026Review
- Mitochondrial DNA leakage in oocytes activates cGAS-STING signaling to drive ovarian aging.Nature aging · 2026Article
- Ovarian Extracellular Matrix Mechanics Regulate Oocyte-Follicle Interactions During Female Reproductive Aging.Aging cell · 2026Article
- The SIRT5-SUCLG2 desuccinylation axis delays ovarian aging via a mitochondrial-epigenetic regulatory mechanism.Nature communications · 2026Article
- Cellular Senescence and Aging: Mechanisms, Disease Convergence, and Therapeutic Frontiers.MedComm · 2026Review
- Article
- VDR-Spermidine Axis Protects Against Age-Related Granulosa Cell Dysfunction and Follicular Decline via DNMTs-Mediated p53 Methylation.International journal of biological sciences · 2026Article
- Repair of female reproductive function by GDF-9-overexpressing extracellular vesicles via ACVR1B/SMAD2 regulation in ovarian granulosa.Science advances · 2025Article
- Review
- A biomimetic senotherapy replenishing MAT2A promotes wound regeneration in preclinical models.Nature communications · 2025Article
- Abnormal cholesterol-cholesteryl ester metabolism impairs mouse oocyte quality during ovarian aging.Cellular & molecular biology letters · 2025Article
- Fosl2 facilitates chromatin accessibility to determine developmental events during follicular maturation.Nature communications · 2025Article
- Mevalonate metabolites boost aged oocyte quality through prenylation of small GTPases.Nature aging · 2025Article
- Subcutaneous delivery of icariin via a gelatin methacryloyl (GelMA) hydrogel sustained-release system improves ovarian function in reproductively aged mice.Zoological research · 2025Article
- Mitochondrial Quality Control in Bovine Oocyte Maturation: Mechanisms, Challenges, and Prospects for Enhancing Reproductive Efficiency.Animals : an open access journal from MDPI · 2025Review
- Ferroptosis and Sterol Biosynthesis Dysregulation in Granulosa Cells of Patients with Diminished Ovarian Reserve.Antioxidants (Basel, Switzerland) · 2025Article
- Age-associated accumulation of RAB9 disrupts oocyte meiosis.Aging cell · 2025Article
- Unraveling the metabolic heterogeneity and commonality in senescent cells using systems modeling.Life medicine · 2025Article
- Article
- BDNF secreted by mesenchymal stem cells improves aged oocyte quality and development potential by activating the ERK1/2 pathway.Cell communication and signaling : CCS · 2025Article
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Authors and funding
22 authors at 5 institutions in 2 countries.
Funding
Abstract
With aging, abnormalities during oocyte meiosis become more prevalent. However, the mechanisms of aging-related oocyte aneuploidy are not fully understood. Here we performed Hi-C and SMART-seq of oocytes from young and old mice and reveal decreases in chromosome condensation and disrupted meiosis-associated gene expression in metaphase I oocytes from aged mice. Further transcriptomic analysis showed that meiotic maturation in young oocytes was correlated with robust increases in mevalonate (MVA) pathway gene expression in oocyte-surrounding granulosa cells (GCs), which was largely downregulated in aged GCs. Inhibition of MVA metabolism in GCs by statins resulted in marked meiotic defects and aneuploidy in young cumulus-oocyte complexes. Correspondingly, supplementation with the MVA isoprenoid geranylgeraniol ameliorated oocyte meiotic defects and aneuploidy in aged mice. Mechanically, we showed that geranylgeraniol activated LHR/EGF signaling in aged GCs and enhanced the meiosis-associated gene expression in oocytes. Collectively, we demonstrate that the MVA pathway in GCs is a critical regulator of meiotic maturation and euploidy in oocytes, and age-associated MVA pathway abnormalities contribute to oocyte meiotic defects and aneuploidy.
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