Biomarkers and Mechanisms of Male Infertility: Evaluation of Antioxidant Enzymes and Arachidonic Acid Derivatives in Seminal Plasma from Fertile and Infertile Men

Male infertility accounts for approximately 50% of reproductive failures, yet its diagnosis and understanding of underlying mechanisms remain limited. The present observational case-control study aimed to examine seminal plasma concentrations of prostaglandin E₂ (PGE₂), 6-keto-prostaglandin F_1α (6-keto-PGF_1α), F₂-isoprostane, superoxide dismutase 1 (SOD₁), glutathione peroxidase 1 (GPX₁), nitric oxide synthase 1 (NOS₁), and their ratios, in fertile (n = 22, aged 24-45) and infertile (n = 250, aged 21-47) men, including analyses across specific infertile subgroups, using ELISA assays. Overall, no significant differences were observed between fertile and infertile men. However, subgroup analyses revealed notable differences: PGE₂ levels were elevated in asthenozoospermic compared to normozoospermic infertile men (14.23 µg/mL vs. 3.52 µg/mL, <i>p</i> = 0.030), 6-keto-PGF_1α levels were higher in teratozoospermic compared to azoospermic individuals (184.97 ng/mL vs. 102.49 ng/mL, <i>p</i> = 0.040), and the PGE₂/6-keto-PGF_1α ratio showed the greatest intergroup variability. Correlation analyses indicated associations between antioxidant enzymes, prostaglandins and standard semen parameters. These findings provide novel insights into seminal plasma biochemistry and highlight specific parameters and mechanisms that may contribute to functional impairments in infertile men.