Oxidative Damage, Antioxidant Capacity, and Apoptotic Activation in Varicocele: Biochemical Evidence of Improvement After Surgical Repair.

To evaluate seminal oxidative stress, antioxidant defense, apoptosis-related activity, and Sertoli cell biomarkers in infertile men with grade 3 varicocele versus normozoospermic controls, and to assess postoperative changes after varicocelectomy. This prospective observational case-control study included 39 infertile men with grade 3 clinical varicocele and 44 normozoospermic controls. Seminal plasma levels of Malondialdehyde (MDA), 8-hydroxy-2'-deoxyguanosine (8-OHdG), superoxide dismutase (SOD), glutathione peroxidase-1 (GPx-1), reduced glutathione (GSH), nuclear factor erythroid 2-related factor 2 (NRF2), Kelch-like ECH-associated protein 1 (KEAP1), caspase-3, anti-Müllerian hormone (AMH), and inhibin B were measured by ELISA. Testicular volume, semen parameters, and diagnostic performance were also evaluated. Compared with controls, patients with varicocele had lower testicular volumes and impaired semen parameters. Seminal 8-OHdG and caspase-3 levels were higher, whereas SOD and inhibin B levels were lower. Baseline MDA, GPx-1, GSH, NRF2, KEAP1, and AMH levels did not differ significantly. After varicocelectomy, sperm concentration, total sperm count, progressive and total motility, total motile sperm count, morphology, and round cell count improved significantly. Postoperatively, caspase-3, MDA, and KEAP1 decreased, whereas SOD, GPx-1, GSH, NRF2, and inhibin B increased significantly. 8-OHdG showed a borderline decrease, and AMH remained unchanged. SOD showed the best diagnostic performance. Grade 3 varicocele is associated with oxidative DNA damage, impaired antioxidant defense, increased apoptotic signaling, and altered Sertoli cell-related seminal biomarkers. Varicocelectomy partially restores redox homeostasis, which may contribute to improved spermatogenic function.