Silymarin protects from varicocele-induced damages in testis and improves sperm quality: evidence for E2f1 involvement

Abstract

This study was designed to evaluate the protective effect of silymarin (SMN) on varicocele-induced damage in testis and its effects on sperm parameters and on antioxidant status. Wistar rats were divided into three groups: control-sham, varicocele-induced, and SMN-treated varicocelized (50mg/kg, orally) rats. The sperm count, DNA integrity, and histone-protamine transition was evaluated after 42 days. The antioxidant status was analyzed by determining testicular malondialdehyde (MDA) and total thiol molecules (TTM). The endocrine status of the testicular tissue was estimated by counting the normal Leydig cell distribution/mm² and by determination of serum testosterone. The expression of E2f1 mRNA was analyzed using RT-PCR. Carbohydrate depletion and lipid foci replacement in germinal cells were examined by histochemical analyses. Silymarin rehabilitated the varicocele-induced Leydig cell degeneration and testosterone reduction. In addition, SMN recovered the varicocele-induced reduction of TTM and lowered significantly (P < 0.05) the varicocele-elevated content of MDA. The SMN treatment resulted in a significant (P < 0.05) down-regulation of the VCL-up-regulated E2f1 mRNA. Silymarin-treated animals were protected from varicocele-induced testicular atrophy and these animals showed a significant (P < 0.05) increase in the percentage of seminiferous tubules with positive tubular differentiation, repopulation, and spermiogenesis indices. Furthermore, SMN improved the varicocele-induced carbohydrate reduction in germinal cells. Our data suggest that in addition to oxidative stress, alteration in the testicular endocrine function plays a crucial role in the pathogenesis of varicocele. Moreover, the protective effects of SMN on varicocele-induced damage may reflect its antioxidant property, which may be mediated via the E2f1 transcription factor.

Keywords:

• oxidative stress
• silymarin
• spermatogenesis
• varicocele

Acknowledgments

We wish to thank Mr. Ali Karimi and Mr. Hamed Tabatabaie, and the staffs of Histology and Pharmacology laboratories for their kind technical support.

Declaration of interest: The authors report no declarations of interest.

Author contributions: Designed and performed the experiments and wrote the manuscript: HM; Performed the experiments: MSM; Performed the experiments and wrote the manuscript: MR; Analyzed the data: VS-I.