Deciphering the Role of Oxidative Stress in Male Infertility: Insights from Reactive Oxygen Species to Antioxidant Therapeutics.

Male infertility represents a major health concern, accounting for approximately 50% of all infertility cases in couples. This condition arises from multiple etiologies, with oxidative stress gaining increasing attention in recent studies. During the final stages of sperm maturation, the majority of the cytoplasm is discarded, leaving sperm with a diminished antioxidant defense system, which makes them highly susceptible to the detrimental effects of reactive oxygen species (ROS). ROS can be generated from both intrinsic and extrinsic sources. Intrinsically, ROS are primarily produced by mitochondrial activity, while extrinsic factors include alcohol consumption, smoking, circadian rhythm disruption, gut microbiota imbalance, and leukocyte infiltration. Excessive ROS production leads to DNA damage, apoptosis, and epigenetic modifications in sperm, ultimately impairing sperm motility and contributing to infertility. This review provides a comprehensive examination of ROS sources and examines the mechanisms by which ROS induce sperm damage. Furthermore, it explores the therapeutic potential of antioxidants in mitigating oxidative stress and improving sperm quality.