OXIDATIVE STRESS AND MALE INFERTILITY: MECHANISMS, BIOMARKERS, AND THERAPEUTIC IMPLICATIONS: A COMPREHENSIVE REVIEW

Abstract

Male infertility accounts for approximately 40–50% of all infertility cases worldwide, with oxidative stress (OS) identified as a pivotal etiological contributor in up to 80% of infertile men. This review examines the molecular underpinnings of OS-mediated spermatotoxicity, its clinical manifestations, and emerging diagnostic and therapeutic strategies. A systematic narrative review was conducted utilizing peer-reviewed literature sourced from PubMed, Scopus,  Web of Science, and Google Scholar databases, encompassing publications from 1995 to 2024. Studies addressing reactive oxygen species (ROS) biology, spermatozoa redox physiology, antioxidant defense mechanisms, and clinical interventions were critically appraised and synthesized. Compelling evidence implicates elevated seminal ROS—primarily superoxide anion (O₂•⁻), hydrogen peroxide (H₂O₂), and hydroxyl radical (•OH)—in the pathogenesis of sperm DNA fragmentation, lipid peroxidation of the plasma membrane, and impaired mitochondrial membrane potential. These insults collectively compromise sperm motility, morphology, and fertilization competence. Seminal antioxidant capacity, as measured by total antioxidant capacity (TAC) and specific enzymatic activity (superoxide dismutase, catalase, glutathione peroxidase), is significantly attenuated in infertile cohorts. Oxidative stress represents a central, mechanistically validated axis of male reproductive dysfunction. Its reliable quantification and targeted pharmacological mitigation offer viable clinical avenues for improving assistedreproductive technology (ART) outcomes and natural fertility. Further large-scale randomized trials are warranted to standardize antioxidant supplementation protocols.