Ajani E O, Akhigbe T M, Oyedokun P A, Adegbola C A, Adeyemi D H, Akhigbe R E
Department of Physiology, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria.
Reproductive Biology and Toxicology Research Laboratory, Oasis of Grace Hospital, Osogbo, Osun State, Nigeria.
Toxicol Rep. 2025 Jun 4;14:102064. doi: 10.1016/j.toxrep.2025.102064. eCollection 2025 Jun.
Despite the effectiveness of doxorubicin as a chemotherapeutic agent, it exerts toxicity on non-target organs, including the male reproductive organs. This review synthesizes current evidence on both ferroptotic and non-ferroptotic mechanisms underlying doxorubicin (DOX)-induced male reproductive dysfunction. DOX disrupts testicular function by inducing oxidative stress, lipid peroxidation, mitochondrial dysfunction, and apoptosis, particularly in Leydig, Sertoli, and spermatogenic cells. These effects result in reduced testosterone production, impaired spermatogenesis, and poor semen quality. Additionally, DOX alters the hypothalamic-pituitary-gonadal (HPG) axis and downregulates key enzymes involved in steroidogenesis, exacerbating hormonal imbalances and infertility risks. Emerging research highlights ferroptosis, iron-dependent cell death, as a major contributor to DOX-induced testicular damage, with evidence showing that antioxidant agents like melatonin and zinc oxide nanoparticles may offer protective effects. In addition, the results of this review reveal the necessity of investigating the potential of interventional strategies. This research highlights the need for integrative care approaches prioritizing cancer management and fertility preservation. This review aims to inform healthcare providers, patients, and policymakers about the significant consequences of doxorubicin therapy and open new therapeutic horizons for adjuvant therapies.
尽管阿霉素作为一种化疗药物具有有效性，但它会对包括男性生殖器官在内的非靶器官产生毒性。本综述综合了当前关于阿霉素（DOX）诱导男性生殖功能障碍的铁死亡和非铁死亡机制的证据。DOX通过诱导氧化应激、脂质过氧化、线粒体功能障碍和细胞凋亡来破坏睾丸功能，尤其是在睾丸间质细胞、支持细胞和生精细胞中。这些影响导致睾酮分泌减少、精子发生受损和精液质量不佳。此外，DOX改变下丘脑-垂体-性腺（HPG）轴，并下调参与类固醇生成的关键酶，加剧激素失衡和不孕风险。新出现的研究强调铁死亡，即铁依赖性细胞死亡，是DOX诱导睾丸损伤的主要原因，有证据表明褪黑素和氧化锌纳米颗粒等抗氧化剂可能具有保护作用。此外，本综述的结果揭示了研究干预策略潜力的必要性。这项研究强调了优先考虑癌症管理和生育力保护的综合护理方法的必要性。本综述旨在向医疗保健提供者、患者和政策制定者通报阿霉素治疗的重大后果，并为辅助治疗开辟新的治疗前景。
