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Beyond bleomycin-induced pulmonary toxicity, its male reproductive toxicity remains unanswered 50 years after its approval
  • Ana Lobo de Almeida,
  • Mário Sousa,
  • Rosália Sá
Ana Lobo de Almeida
University of Porto
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Mário Sousa
University of Porto
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Rosália Sá
University of Porto

Corresponding Author:rmsa@icbas.up.pt

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Abstract

Aim: Cancer treatment long-term complications for men include testicular dysfunction and possible infertility. Nonetheless, the evidence for this risk for various chemotherapies is insufficient. This is the case with bleomycin, which, aside from its well-studied lung toxicity, has received little research attention for its effect on male reproduction. This systematic review sought evidence for the effects of bleomycin-cancer treatment on testicular function and fertility. Methods: PubMed and Web of Science were searched using specific search terms, and seven animal studies met all inclusion criteria and provided an analysis of bleomycin gonadotoxicity. Results: Overall, the results suggest that bleomycin is gonadotoxic. It has the same effect on the nuclear DNA integrity of rodent sperm as it does on cancer cells. Bleomycin-induced changes in rodent testis histopathology are most noticeable at seminiferous tubule structure level. Bleomycin also significantly decreases rodents´ seminal conventional parameters and testosterone levels, the latter of which is consistent with increased induced degeneration of Leydig cells. Seminiferous tubule necrosis and alterations in tunica albuginea thickness in rodent testis are signs of a bleomycin-induced inflammatory process similar to the pulmonary one. Conclusion: More research, particularly human research, is required to provide strong evidence on how bleomycin affects human testicular function, including hormone function; and whether is gonadotoxic, whether it has a transient or permanent effect; how it may affect offspring; and how it can be reduced. Despite this, the current findings have important implications for clinicians in counseling patients about fertility risk and guiding requirements for fertility preservation strategies.