Assessment of Spermatogenesis Following Bleomycin Treatment in Male Rat Model: The Damage and Recovery Process.
Bayram Hale, Çakil Yaprak Dönmez, Saraç Ayşe, Altiner Necdet
Abstract
Bleomycin, commonly used in the treatment of various malignant tumors, has also been associated with gonadal toxicity and reduced fertility. This study aims to evaluate the effects of bleomycin on the male reproductive system. Twelve-week-old male rats were randomly divided into four groups: Control, B-0, B-60, and B-120. The treatment groups received 15mg/kg of bleomycin intraperitoneally twice a week for three weeks. Following treatment, the rats were sacrificed on days 0, 60, and 120. Body weight and sperm concentration decreased significantly in the B-0 group compared to the control group, while they showed a partial increase in the B-60 and B-120 groups. Sperm DNA fragmentation was found to be significantly higher in the B-0 group compared to the control group, similar to the control group in the B-60 and B-120 groups. In the B-0 group, marked degeneration of the seminiferous tubules and thinning of the germinal epithelium were observed; the B-60 and B-120 groups improved to some extent. No significant differences were found between the groups in serum testosterone, MDA, and TAS levels, or in the expression levels of the Bax, Bcl2, Caspase-3, HO-1, iNOS, and Nrf2 genes. While NO levels increased in the B-0 group, they decreased to levels similar to those of the control group in the B-60 and B-120 groups. In conclusion, bleomycin causes significant but largely reversible damage to the male reproductive system, particularly affecting sperm parameters and testicular histology. However, the absence of fertilization and pregnancy assessment should be considered when interpreting the findings.
Key Findings
- Bleomycin treatment significantly decreased body weight and sperm concentration immediately after treatment (B-0 group), with partial recovery observed at 60 and 120 days post-treatment.
- Sperm DNA fragmentation was significantly higher in the B-0 group but returned to control levels in the B-60 and B-120 groups, indicating reversible DNA damage.
- No significant changes were observed in serum testosterone, MDA, TAS levels, or expression of oxidative stress and apoptosis-related genes including Nrf2, HO-1, Bax, Bcl2, Caspase-3, and iNOS, although nitric oxide levels were elevated immediately after treatment and normalized later.
Clinical Significance
The study demonstrates that bleomycin induces oxidative stress-related damage to the male reproductive system that is largely reversible, highlighting the importance of monitoring and potentially managing reproductive toxicity in patients undergoing bleomycin chemotherapy.
Citation
Bayram Hale, Çakil Yaprak Dönmez, Saraç Ayşeet al.. Assessment of Spermatogenesis Following Bleomycin Treatment in Male Rat Model: The Damage and Recovery Process. Reproductive toxicology (Elmsford, N.Y.). 2026-Aug-29.