• Effects of Busulfan on Testis Tissue and Epididymal Sperm of Adult Mice: A Comprehensive Review
  • Maryam Alsadat Hashemi,1,* Hossein Khanafereh,2 Parva Nasimi,3
    1. Islamic Azad University, Abhar Branch, Faculty of Agricultural and Environmental Sciences Agricultural engineering, green space design engineering
    2. Imam Jafar Sadegh Laboratory and Research Center
    3. Regensburg University, Prof. Brembs Laboratory, Germany


  • Introduction: Busulfan, a chemotherapeutic agent widely employed in clinical settings, has been associated with detrimental impacts on male reproductive health. This comprehensive review aims to provide an in-depth analysis of the existing literature on the side effects of busulfan treatment on testis tissue and epididymal sperm in adult mice. Understanding the mechanisms and consequences of busulfan-induced damage to the male reproductive system is of paramount importance in addressing potential reproductive concerns in patients undergoing chemotherapy.
  • Methods: A systematic search of scientific databases, including PubMed, Scopus, and Web of Science, was conducted to identify relevant studies published until September 2023. The eligibility criteria for inclusion encompassed research focusing on the effects of busulfan on testis tissue and epididymal sperm in adult male mice. The review rigorously evaluated methodological aspects such as busulfan dosages, administration routes, treatment durations, and the assessment tools used to gauge testicular and sperm damage.
  • Results: Numerous investigations have shed light on the adverse effects of busulfan on the male reproductive system. The findings consistently demonstrate that busulfan, even at clinical doses, induces significant damage to testis tissue. Histological examinations reveal pronounced alterations, including disruption of seminiferous tubules, germ cell depletion, and impaired spermatogenesis. These detrimental effects are accompanied by an increase in apoptotic markers within the testicular tissue. Moreover, busulfan treatment has a substantial impact on epididymal sperm quality. Studies consistently report a reduction in sperm count, motility, and viability following busulfan exposure. Notably, this damage occurs at low doses of busulfan, suggesting a heightened vulnerability of sperm cells to the drug's cytotoxic effects. The compromised sperm quality is further underscored by an increase in DNA damage, chromatin abnormalities, and elevated oxidative stress markers in epididymal sperm.
  • Conclusion: This comprehensive review underscores the deleterious consequences of busulfan treatment on testis tissue and epididymal sperm in adult mice. Busulfan, even at clinical doses, leads to significant histopathological alterations in testis tissue, characterized by seminiferous tubule disruption and germ cell loss. The drug's cytotoxic effects extend to epididymal sperm, resulting in reduced sperm count, motility, and viability. Additionally, the induction of DNA damage, chromatin abnormalities, and oxidative stress in sperm highlights the multifaceted nature of busulfan's impact on male reproductive health. The findings from this review emphasize the importance of careful consideration of the potential reproductive consequences of busulfan treatment in clinical settings. Furthermore, they underscore the need for developing strategies to mitigate busulfan-induced testicular and sperm damage, especially in individuals of reproductive age undergoing chemotherapy.
  • Keywords: Busulfan, testis tissue, epididymal sperm, cytotoxicity, apoptosis.