Dose-dependent protective effects of p-coumaric acid on testicular ischemia/reperfusion injury in a mouse model of testicular torsion

Abstract

Testicular torsion triggers ischemia/reperfusion (I/R) injury that drives oxidative stress, germ cell apoptosis, and long-term impairment of spermatogenesis and fertility. This study investigated dose-dependent protective effects of p-coumaric acid (p-CA), a phenolic molecule with well-documented antioxidant, anti-inflammatory, and anti-apoptotic properties, in a mouse model of testicular torsion. Forty adult male mice underwent 2 h of 720° unilateral testicular torsion, followed by detorsion. Animals were randomly assigned to sham, torsion/detorsion (T/D), and three T/D + p-CA groups. Thirty minutes before detorsion, the mice received intraperitoneal p-CA at 50, 100, or 200 mg/kg. Sperm quality (concentration, motility, and kinematics) was evaluated in the right testis and epididymis after a 30-day recovery period. Fertility outcomes, testicular histology, oxidative stress markers, and molecular indicators of apoptosis were also assessed. The T/D procedure markedly diminished sperm quality, lowered antioxidant capacity (TAC, SOD, GPx), reduced hormone levels, elevated malondialdehyde (MDA), and increased apoptotic markers (Bax, caspase-3). Administration of p-CA attenuated these changes in a dose-dependent manner. Doses of 100 and 200 mg/kg most effectively improved sperm parameters, enhanced antioxidant defenses, preserved seminiferous tubule architecture, and suppressed apoptosis. Only moderate improvement was observed with the 50 mg/kg dose. Collectively, the results suggest that p-CA exerts robust protective effects against testicular ischemia/reperfusion injury, preserving spermatogenesis and fertility. To our knowledge, this is the first study to characterize the dose-dependent protective effects of p-CA in a mouse model of testicular torsion/detorsion, integrating detailed sperm kinematics, molecular apoptotic profiling, and actual fertility outcomes within a single experimental framework. These findings extend existing knowledge on phenolic antioxidants and highlight the translational potential of p-CA as a perioperative adjunct in the clinical management of testicular torsion.