Background: Cyclophosphamide, a widely used chemotherapy drug, despite its therapeutic benefits, induces oxidative stress and causes reproductive toxicity. This study evaluated the effect of selenium, a potent antioxidant, on sperm DNA integrity and nuclear maturation in NMRI mice following cyclophosphamide treatment. Materials and Methods: Thirty-two adult male NMRI mice were randomly divided into four groups: control, cyclophos- phamide (intraperitoneal injection, 100 mg/kg, once a week), selenium (intraperitoneal injection, 1 mg/kg, every day), and cyclophosphamide + selenium. Treatments were administered for 35 days. After dissecting the mice, the caudal region of the epididymis was isolated in Ham's F10 culture medium. Sperm were extracted and assessed for integrity of DNA double- stranded structure using acridine orange staining and for nu- clear maturity using aniline blue staining. Data were analyzed using SPSS software with one-way ANOVA and Tukey’s test; differences were considered statistically significant at P<0.05. Results: A significant decrease in the mean sperm nuclear ma- turity (P<0.05) and integrity of DNA double-stranded structure (P<0.001) was observed in the cyclophosphamide group com- pared to the control group. These side effects were compen- sated for in the cyclophosphamide + selenium group compared to the cyclophosphamide group. Conclusion: Our results showed that cyclophosphamide im- pairs sperm nuclear maturation and DNA integrity in NMRI mice by inducing oxidative stress. However, co-administration of selenium effectively reduced these adverse effects, highlight- ing its potential as a protective agent against cyclophospha- mide-induced reproductive toxicity.
