Epigenetic Codes of Cumulus Oophorus Extracellular Vesicles in Oocyte Sufficiency: Programming of Oocyte Peripheral Memory and Determination of Embryonic Developmental Potential

Aim and Significance: Oocyte developmental competence is closely associated with bidirectional communication between the oocyte and the surrounding cumulus oophorus cells. Extracellular vesicles (EVs) play an important role in this communication by transferring proteins, microRNAs (miRNAs), and other bioactive molecules. This review aims to evaluate the roles of cumulus cellderived EVs in the epigenetic regulation of oocyte developmental competence and embryonic developmental potential, as well as their possible clinical applications. Materials and Methods: This narrative review examines findings of the literature on the molecular cargo of cumulus cell- and follicular fluid-derived EVs, their effects on oocyte developmental competence, and their potential applications in assisted reproductive technologies. Findings: The reviewed studies indicate that EVs may influence oocyte developmental competence through three principal mechanisms: miRNA-mediated regulation of gene expression, metabolic and antioxidant support, and modulation of cellular signaling pathways including MAPK signaling. Small and large EV subpopulations exhibit differences in their molecular cargo and biological functions. Furthermore, alterations in EV cargo associated with aging and conditions such as polycystic ovary syndrome may provide molecular indicators related to oocyte quality. Conclusion: Cumulus cell-derived EVs may contribute to intercellular communication and epigenetic regulatory processes influencing oocyte developmental competence. Characterizing EV cargo as potential biomarkers and using it in in vitro oocyte maturation systems may offer promising applications in assisted reproductive technologies. However, further research is required to establish their clinical effectiveness. Keywords: Cumulus Cells; Extracellular Vesicles; Oocytes; Epigenesis; Genetic.