Epigenetic reprogramming and oocyte quality: Resetting the biological clock in the female reproductive system
DOI:
https://doi.org/10.37800/RM.2.2026.734Keywords:
epigenetic clock, oocyte aging, DNA methylation, chromosomal instability, epigeneticAbstract
Relevance: Age-related decline in oocyte quality remains an unresolved problem in reproductive medicine. With increasing age at childbearing in developed countries, more and more women face infertility due to decreased oocyte competence. Understanding the epigenetic mechanisms of oocyte aging offers opportunities for restoring reproductive potential.
The study aimed to examine and summarize current data on epigenetic mechanisms of oocyte aging and to evaluate the potential of epigenetic reprogramming technologies to restore oocyte quality.
Materials and Methods: Publications in PubMed, Scopus, and Web of Science from 2013 to 2026 were analyzed using the following keywords: epigenetic clock, oocyte aging, DNA methylation, chromosomal instability, aneuploidy, and epigenetic reprogramming.
Results: Oocyte aging is accompanied by specific changes in DNA methylation: global hypomethylation and focal hypermethylation of genes controlling chromosome segregation and embryonic development. Imprinted genes are particularly vulnerable. The epigenetic age of cumulus cells correlates with oocyte developmental potential and IVF outcomes. The possibility of reversing age-related epigenetic changes has been experimentally demonstrated: transfer of somatic cell nuclei into the cytoplasm of young oocytes restores the developmental potential of aging nuclei; transient expression of Yamanaka factors induces partial reprogramming, erasing age-related methylation marks.
Conclusion: Epigenetic reprogramming is a promising strategy for restoring oocyte quality. Experimental data confirm the possibility of reversing age-related epigenetic changes and reducing aneuploidy. Clinical translation requires addressing safety issues, preserving the methylation of imprinted genes, and developing effective delivery systems. Success in this area could fundamentally change reproductive medicine, enabling the realization of reproductive potential regardless of age.
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