Curcumin-Loaded Milk-Derived Exosomes Improve the Developmental Competence of Yak Oocytes by Regulating Mitophagy

Yaks are a distinctive livestock species native to the Qinghai-Tibet Plateau. However, the low in vitro maturation rate of their oocytes significantly limits the efficiency of assisted reproductive technologies. Curcumin (CUR), known for its bioactive functions, including antioxidant and anti-inflammatory properties, suffers from low water solubility and bioavailability, which restricts its practical applications. This study aimed to develop a curcumin-loaded bovine milk-derived exosome nanodelivery system (CUR-mEXOs) and investigate its effects on the in vitro maturation of yak oocytes and the embryonic development of parthenogenetic embryos, leveraging its natural biocompatibility and targeted delivery properties. The results indicated that the isolated mEXOs exhibited typical exosome morphology and nanoscale particle size characteristics and were effectively internalized by the oocytes. During in vitro maturation, treatment with 10 μM CUR produced optimal outcomes. Compared to free CUR, CUR-mEXOs significantly enhanced the cumulus expansion index and the rate of first polar body expulsion, reduced intracellular ROS accumulation and mitochondrial superoxide levels, and improved mitochondrial function and spindle morphology, while simultaneously upregulating the expression of factors related to mitochondrial autophagy and oocyte maturation. Following intervention with the mitochondrial autophagy inhibitor CsA, the promotive effect of CUR-mEXOs was significantly diminished, leading to increased blastocyst apoptosis and a decrease in the total cell count. In summary, CUR-mEXOs can enhance the quality of in vitro maturation of yak oocytes and their embryonic developmental capacity following parthenogenesis by regulating mitochondrial autophagy. This study established an experimental foundation for optimizing the in vitro maturation system of yak oocytes and developing strategies for the delivery of natural bioactive substances. Additionally, this study provides a theoretical basis for enhancing the efficiency of assisted reproductive technologies in yaks.