Age-Related Decline of Male Fertility: Mitochondrial Dysfunction and the Antioxidant Interventions

Abstract

Mitochondria are structurally and functionally unique organelles in male gametes. Apparently, as the only organelles remaining in mature sperm, mitochondria not only produce adeno-sine triphosphate (ATP) through oxidative phosphorylation (OXPHOS) to support sperm mobility, but also play key roles in regulating reactive oxidation species (ROS) signaling, calcium homeostasis, steroid hormone biosynthesis, and apoptosis. Mitochondrial dysfunction is often associated with the aging process. Age-dependent alterations of the epididymis can cause alterations in sperm mitochondrial functioning. The resultant cellular defects in sperm have been implicated in male infertility. Among these, oxidative stress (OS) due to the overproduction of ROS in mitochondria may represent one of the major causes of these disorders. Excessive ROS can trigger DNA damage, disturb calcium homeostasis, impair OXPHOS, disrupt the integrity of the sperm lipid membrane, and induce apoptosis. Given these facts, scavenging ROS by antioxidants hold great potential in terms of finding promising therapeutic strategies to treat male infertility. Here, we summarize the progress made in understanding mitochondrial dysfunction, aging, and male infertility. The clinical potential of antioxidant interventions was also discussed.