Protective Role of All-Trans Retinoic Acid Against Ipsilateral Testicu-lar Ischemia-Reperfusion Injury in Male Wistar Rats.

OBJECTIVE: Testicular torsion (TT) may cause testicular necrosis. Although restoration of blood flow is essential to prevent testicular loss, reperfusion may induce testicular ischemia-reperfusion injury (TIRI), leading to testicular damage and potentially long-term infertility. All-trans reti-noic acid (ATRA) has been shown to enhance the transcrip-tion of antioxidant enzymes and anti-apoptotic proteins, inhibit NF-κB-mediated transcription of inflammatory cyto-kines, and support germ-cell differentiation and spermato-genesis. This study investigated the protective effect of ATRA on the ipsilateral testis following unilateral testicular torsion/detorsion. METHODS: Twenty-four male Wistar rats were divided into four groups (n=6): Sham, Torsion/Detorsion (TD), AT-RA+TD (7.5mg/kg administered 3 days before TIRI induc-tion), and TD+ATRA (7.5mg/kg administered 3 days after TIRI induction). Torsion was induced for 1 hour and was followed immediately by detorsion. RESULTS: TD reduced the levels of reproductive hormones (testosterone and inhibin), Bcl-2, sperm indices, SOD, CAT, GPx, GST, GSH, and total protein, with concomitant increas-es in testicular MDA, NO, TNF-α, MPO, IL-6, NF-κB, Bax, caspase-3, DFI, and 8-OHdG levels. Histological evaluation of TD rats revealed reduced spermatogenesis indices, disrup-tion of the seminiferous tubules, germ-cell loss, and vascular congestion. ATRA treatment significantly improved antioxi-dant enzyme activity, downregulated NF-κB and Bax signal-ing, restored reproductive hormones and sperm parameters, and protected testicular and epididymal structures. CONCLUSION: ATRA protects against ipsilateral testicu-lar damage following torsion/detorsion, as shown by res-toration of depleted antioxidant enzymes, downregulation of inflammatory and pro-apoptotic markers, and enhance-ment of spermatogenesis and hormonal balance. These findings support the potential role of ATRA in preserving fertility after testicular torsion/detorsion.