Significance: Currently 10%-15% of couples in reproductive age face infertility issues. More importantly, male factor contributes to 50% of these cases (either alone or in combination with female causes). Among various reasons, impaired sperm function is the main cause for male infertility. Furthermore, mitochondrial dysfunction and oxidative stress due to increased reactive oxygen species (ROS) production, particularly of mitochondrial origin, are believed to be the main contributors. Recent Advances: Mitochondrial dysfunction, particularly due to increased ROS production, has often been linked to impaired sperm function/quality. For decades, different methods and approaches have been developed to assess mitochondrial features that might correlate with sperm functionality. This connection is now completely accepted, with mitochondrial functionality assessment used more commonly as a readout of sperm functionality. More recently, mitochondria-targeted compounds are on the frontline for both assessment and therapeutic approaches. Critical Issues: In this review, we summarize the current methods for assessing key mitochondrial parameters known to reflect sperm quality as well as therapeutic strategies using mitochondria-targeted antioxidants aiming to improve sperm function in various situations, particularly after sperm cryopreservation. Future Directions: Although more systematic research is needed, mitochondria-targeted compounds definitely represent a promising tool to assess as well as to protect and improve sperm function. Antioxid. Redox Signal. 37, 451-480.
Keywords: ROS detection; mitochondria-targeted antioxidants; mitochondria-targeted fluorescent probes; mitochondrial function; mitochondrial membrane potential; oxidative stress; sperm function.