Background: Cyclophosphamide is used in cancer treatment, but it also disturbs the testis tissue and the process of spermatogenesis through increasing oxidative stress. Objective: This study aimed to investigate silymarin’s effect on testicular histological alterations, spermatogenesis indexes, and daily sperm production in adult male mice following cyclophosphamide treatment. Materials and Methods: 24 NMRI male mice (37 ± 2 gr) were divided into 4 groups (n = 6/each): control; cyclophosphamide (100 mg/kg bw/wk, i.p); silymarin (200 mg/kg bw/interval day, i.p) and cyclophosphamide (100 mg/kg) + silymarin (200 mg/kg). After 35 days of treatment, daily sperm production, Johnsen’s score, and spermatogenesis indexes were evaluated. Also, the testis tissue was studied using a stereological technique. Results: A significant decrease in the total volume of the testis (43.18 ± 4.10), the volume of seminiferous tubules (34.09 ± 2.84) and interstitial tissue (9.08 ± 1.65), germinal epithelial height (24.86 ± 3.10), length (0.77 ± 0.10) and diameter of seminiferous tubules (127.10 ± 2.94), the number of spermatogonia (3.58 ± 0.51), spermatocyte (11.57 ± 1.34), elongated spermatid (20.66 ± 2.31), round spermatid (19.25 ± 2.10), Sertoli (1.78 ± 0.64) and Leydig cells (1.80 ± 0.15), spermatogenesis indexes (SPI: 44.00 ± 2.19; TDI: 51.50 ± 3.78; SCI: 14.96 ± 2.92; MI: 0.86 ± 0.02), Johnsen’s score (5.08 ± 0.03), and the daily sperm production (9.61 ± 2.39) was observed in the cyclophosphamide group compared to the control group (p < 0.01). The mentioned parameters were significantly increased in the cyclophosphamide + silymarin group compared to the cyclophosphamide group (p < 0.01). These parameters did not significantly differ between the control and silymarin groups (p > 0.05). Conclusion: According to the findings of this study, silymarin as an antioxidant can reduce the negative effects of cyclophosphamide on testis tissue, spermatogenesis indexes, and daily sperm production.
