The long-term protective effect of tadalafil on spermatogenesis following testicular ischemia-reperfusion injury in a rat model

Abstract

Background Testicular torsion is a urological emergency in which misdiagnosis and inappropriate treatment can lead to testicular atrophy and male infertility owing to ischemia-reperfusion injury (IRI). Although experimental studies of testicular torsion have been preceded, promising therapeutic agents based on the long-term effect for spermatogenesis have not been identified in testicular ischemia reperfusion injury (IRI) animal model. Tadalafil, one of the phosphodiesterase-5 inhibitors commonly used in the treatment of erectile dysfunction, has recently reported a protective effect against IRI in several organs. In this study, we evaluated the long-term protective effect of tadalafil for spermatogenesis in a rat testicular IRI model. Methods Forty-eight adolescent Sprague–Dawley rats were divided into 6 groups (A-F). Sham operation was performed in group A. Group B received surgical 720-degree torsion of the left testis without any medication. Groups C, D, E, and F were operated surgical torsion with tadalafil at varying doses (0.3 mg/kg, 1.0 mg/kg) and durations (single or daily administration for 4 weeks). Detorsion was performed after 3 hour of torsion in all rats except the sham group. Four weeks after operation, both testes were evaluated of spermatogenesis using Johnsen scoring. To evaluate the protective effect of tadalafil against oxidative stress by IRI, malondialdehyde (MDA) and superoxide dismutase (SOD) level were analyzed via ELISA in both testes 4 hour after detorsion in the same experiments as in group A, B, and C. Results For the evaluation of spermatogenesis according to doses, the groups with high-dose tadalafil showed a higher Johnsen scores than low-dose counterparts. The groups with daily administration for 4weeks were observed a higher Johnsen scores than those given a single administration. Furthermore, molecular markers (MDA and SOD) related with oxidative stress and histopathologic findings showed remarkable improvement after tadalafil administration. Conclusion Tadalafil alleviated long-term deterioration of spermatogenesis and oxidative stress by restoring antioxidant status after testicular IRI rat model. Furthermore, it demonstrated a protective effect against testicular IRI in a time- and dose-dependent manner.

Long-term protective effect of tadalafil on spermatogenesis following testicular ischemia-reperfusion injury in a rat model

“…Previously, we conducted a study on adolescent rats to identify the ischemic duration that would result in serious long-term histopathologic changes after testicular IRI. Histopathologic analysis performed four weeks after testicular IRI confirmed there was serious deterioration in spermatogenic activity after three hours of ischemia, but not after shorter ischemic durations [31]. For the current study we therefore selected three hours of ischemia as the duration of torsion in order to study the long-term effects on spermatogenesis.…”

“…The rats were then euthanized using carbon dioxide gas or cervical dislocation. In a previous study with a rat testicular torsion model, we found that testicular damage was aggravated in an ischemic time-dependent manner, and that serious deterioration of spermatogenic activity developed three hours after ischemia [31]. Therefore, three hours of ischemia was selected as the torsion duration period for the present study.…”