ArticleAging cell2022
Loss of heterochromatin and retrotransposon silencing as determinants in oocyte aging.
Article in Aging cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 41 citations in OpenAlex.
- Endocrine and Molecular Mechanisms of Oocyte Aging: From Gonadotropin Signaling to Metabolic and Microenvironmental Dysfunction.Current issues in molecular biology · 2026Review
- Maternal age as a driver of genome instability: mechanisms linking aneuploidy, mutagenesis and mitochondrial dysfunction.Archives of toxicology · 2026Review
- R-loop homeostasis at transposable elements safeguards transcriptional silencing in replication-quiescent oocytes.Nature communications · 2026Article
- Critical roles of m6A demethylase FTO in ovarian aging.Biogerontology · 2026Review
- Ribosome dysregulation and intervention in age-related infertility.Cell reports. Medicine · 2025Article
- Targeting DNA damage in ageing: towards supercharging DNA repair.Nature reviews. Drug discovery · 2025Review
- The dynamics of DNA methylation, histone methylation and acetylation during oocyte aging in mammalian species and possible interventions to regulate them.Journal of assisted reproduction and genetics · 2025Review
- Article
- Inhibition of ferroptosis counteracts the advanced maternal age-induced oocyte deterioration.Cell death and differentiation · 2025Article
- Autonomous follicle quality control mechanisms: innate immune signaling capabilities of granulosa cells.Reproduction (Cambridge, England) · 2025Review
- Mitochondrial Oxidative Phosphorylation Alterations in Placental Tissues from Early- and Late-Onset Preeclampsia.International journal of molecular sciences · 2025Article
- Age-associated accumulation of RAB9 disrupts oocyte meiosis.Aging cell · 2025Article
- Hallmarks of female reproductive aging in physiologic aging mice.Nature aging · 2024Review
- Roles of chromatin and genome instability in cellular senescence and their relevance to ageing and related diseases.Nature reviews. Molecular cell biology · 2024Review
- Article
- Diminished NAD+ levels and activation of retrotransposons promote postovulatory aged oocyte (POAO) death.Cell death discovery · 2024Article
- Oocyte Aging: A Multifactorial Phenomenon in A Unique Cell.Aging and disease · 2024Review
- Depletion of SAM leading to loss of heterochromatin drives muscle stem cell ageing.Nature metabolism · 2024Article
- Impaired neuron differentiation in GBA-associated Parkinson's disease is linked to cell cycle defects in organoids.NPJ Parkinson's disease · 2023Article
- Epigenetic aging in oocytes.Aging · 2023Article
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mammalian oocyte quality reduces with age. We show that prior to the occurrence of significant aneuploidy (9M in mouse), heterochromatin histone marks are lost, and oocyte maturation is impaired. This loss occurs in both constitutive and facultative heterochromatin marks but not in euchromatic active marks. We show that heterochromatin loss with age also occurs in human prophase I-arrested oocytes. Moreover, heterochromatin loss is accompanied in mouse oocytes by an increase in RNA processing and associated with an elevation in L1 and IAP retrotransposon expression and in DNA damage and DNA repair proteins nuclear localization. Artificial inhibition of the heterochromatin machinery in young oocytes causes an elevation in retrotransposon expression and oocyte maturation defects. Inhibiting retrotransposon reverse-transcriptase through azidothymidine (AZT) treatment in older oocytes partially rescues their maturation defects and activity of the DNA repair machinery. Moreover, activating the heterochromatin machinery via treatment with the SIRT1 activating molecule SRT-1720, or overexpression of Sirt1 or Ezh2 via plasmid electroporation into older oocytes causes an upregulation in constitutive heterochromatin, downregulation of retrotransposon expression, and elevated maturation rates. Collectively, our work demonstrates a significant process in oocyte aging, characterized by the loss of heterochromatin-associated chromatin marks and activation of specific retrotransposons, which cause DNA damage and impair oocyte maturation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.