Huang Rufei, Xia Huan, Lin Wanqing, Wang Zhaoyang, Li Lu, Deng Jingxian, Ye Tao, Li Ziyi, Yang Yan, Huang Yadong
Department of Cell Biology, Jinan University, Guangzhou 510632, China.
Guangdong Province Key Laboratory of Bioengineering Medicine, Guangzhou 510632, China.
Cells. 2024 Dec 6;13(23):2016. doi: 10.3390/cells13232016.
Cancer treatments, including cytotoxic therapy, often result in male infertility, necessitating the development of safe and effective strategies to preserve male reproductive potential during chemotherapy. Notably, our study uncovers the potential of repurposing riluzole, an FDA-approved drug for amyotrophic lateral sclerosis (ALS), in enhancing spermatogenesis. Hence, this research aims to explore the feasibility of utilizing riluzole to alleviate male infertility induced by busulfan (BSF), a commonly used chemotherapy drug. We established a BSF-induced oligospermia model in 4-week-old male mice and found that riluzole could effectively counter the detrimental effects of BSF on sperm production in mice with oligospermia. By restoring blood-testis barrier (BTB) functionality, riluzole improves sperm quality and reduces testicular atrophy. Through transcriptomic and molecular docking analyses, we identify transient receptor potential canonical subfamily member 5 (TRPC5) as a potential target for riluzole-mediated regulation of blood-testis barrier function. These findings propose riluzole as a promising therapeutic option for chemotherapy-induced male infertility, thereby addressing the fertility challenges associated with cancer treatments. Moreover, repurposing riluzole could streamline the drug development process, providing a cost-effective approach with reduced risk compared to developing entirely new drugs.
包括细胞毒性疗法在内的癌症治疗通常会导致男性不育，因此需要开发安全有效的策略来在化疗期间保留男性生殖潜力。值得注意的是，我们的研究发现了重新利用利鲁唑（一种经美国食品药品监督管理局批准用于治疗肌萎缩侧索硬化症（ALS）的药物）来增强精子发生的潜力。因此，本研究旨在探讨利用利鲁唑缓解由常用化疗药物白消安（BSF）引起的男性不育的可行性。我们在4周龄雄性小鼠中建立了白消安诱导的少精子症模型，发现利鲁唑可以有效对抗白消安对少精子症小鼠精子产生的有害影响。通过恢复血睾屏障（BTB）功能，利鲁唑提高了精子质量并减少了睾丸萎缩。通过转录组学和分子对接分析，我们确定瞬时受体电位香草酸亚家族成员5（TRPC5）是利鲁唑介导的血睾屏障功能调节的潜在靶点。这些发现表明利鲁唑是化疗诱导的男性不育的一种有前景的治疗选择，从而解决了与癌症治疗相关的生育挑战。此外，重新利用利鲁唑可以简化药物开发过程，提供一种比开发全新药物更具成本效益且风险更低的方法。
