Human amniotic mesenchymal stem cell-derived extracellular vesicles improve oocyte quality and embryonic development by increasing antioxidant capacity in aged mice.

BACKGROUND: Age-related decline in oocyte quality is a significant factor in reduced fertility. This study aimed to evaluate the role of human amniotic mesenchymal stem cell-derived extracellular vesicles (hAMSC-EVs) on oocytes in aged mice and to elucidate the underlying molecular mechanisms. METHODS: An appropriate concentration of hAMSC-EVs was added to the in vitro maturation culture medium of mouse GV-stage aged oocytes. To assess nuclear maturation, the rate of first polar body extrusion and spindle morphology of MII-stage oocytes were evaluated. Following in vitro fertilization (IVF), fertilization rates and blastocyst formation rates were measured to assess cytoplasmic maturation. Intracellular oxidative stress levels were determined by measuring reactive oxygen species (ROS) and glutathione (GSH) levels, while mitochondrial function was evaluated by assessing mitochondrial membrane potential and ATP production. RESULTS: Compared with the untreated aged oocytes, treatment with hAMSC-EVs significantly improved the maturation of aged oocytes and promoted oocyte fertilization and early embryonic development after IVF. Mechanistically, hAMSC-EV was taken up by the cumulus-oocyte complex and increased the expression of SOD2, GPX, and HO-1 in oocytes by regulating the Keap1/Nrf2 pathway, which was significantly associated with attenuated ROS and increased GSH levels and improved mitochondrial function in aged oocytes. CONCLUSIONS: These findings offer a novel theoretical and experimental foundation for the clinical management of age-related diminished ovarian reserve.