MitoQ as a Mitochondria-Targeted Antioxidant in Sperm Cryopreservation: An Updated Review on Its Mechanisms, Efficacy, and Future Perspectives

Sperm cryopreservation is a key technique in assisted reproductive technologies (ART), livestock breeding, fertility preservation, and wildlife conservation. However, the freeze-thaw process induces significant oxidative stress through the production of reactive oxygen species (ROS) by mitochondria, which can lead to impaired sperm motility, membrane damage, DNA fragmentation, and reduced fertilization potential. MitoQ is a mitochondria-targeted antioxidant consisting of a ubiquinone moiety conjugated to triphenylphosphonium (TPP⁺). MitoQ selectively accumulates in the mitochondrial matrix, where it efficiently scavenges reactive oxygen species (ROS) at their point of origin. This targeted action helps preserve mitochondrial function, sustain ATP production, and inhibit apoptotic signaling. Extensive experimental evidence across diverse species, including bulls, rams, boars, humans, dogs, and goats, shows that MitoQ supplementation during cryopreservation enhances post-thaw sperm viability, motility, membrane integrity, and DNA stability. Optimal dosing between 50 and 150 nM achieves these benefits without cytotoxicity, although higher doses may paradoxically increase oxidative damage. Compared to conventional antioxidants, MitoQ offers superior mitochondrial protection and enhanced preservation of sperm bioenergetics. Future directions involve exploring synergistic combinations with other cryoprotectants, advanced delivery systems such as nanoparticles and hydrogels, and detailed mechanistic studies on long-term effects. Overall, MitoQ represents a promising adjunct for improving sperm cryopreservation outcomes across clinical, agricultural, and conservation settings.