Curcumin promotes spermatogenesis in mice with cryptorchidism by regulating testicular protein O-GlcNAcylation

The findings indicated that cryptorchidism had a detrimental impact on reproductive function, evident by decreased testicular coefficient, cessation of sperm production, abnormal testicular tissue morphology, and hormonal imbalances. Curcumin treatment mitigated these abnormalities, with the most significant improvement observed at a dosage of 100 mg/kg, without substantial adverse effects on other organs. Mechanistic studies revealed that cryptorchidism reduced testicular protein <i>O</i>-GlcNAcylation levels, while curcumin supplementation effectively increased this modification in a dose-dependent manner. Molecular docking and UDP-GlcNAc analyses further demonstrated that curcumin restores <i>O-GlcNAc</i>ylation homeostasis by inhibiting OGA via high-affinity binding and enhancing OGT activity through substrate accumulation, synergistically rebalancing <i>O-GlcNAc</i>ylation dynamics. This study uncovers a novel mechanism by which curcumin facilitates spermatogenesis through the regulation of testicular protein <i>O</i>-GlcNAcylation, providing a significant theoretical foundation for its utilization in male reproductive health.