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Updated: Jan 28, 2026

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布苏尔加环胺诱导的精子生成功能障碍和恢复:一个动态变化前景

Tianyu Li¹, Zhichen Tang², Yaping Song²

¹West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, Sichuan, 610041, PR China; Laboratory of Molecular Translational Medicine, Center for Translational Medicine, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, 610041, PR China.

Toxicology letters

|January 26, 2026

概括

布苏尔-cyclophosphamide (BuCy) 化学疗法导致男性不孕. 这项研究详细介绍了BuCyCy.

科学领域:

生殖生物学生殖生物学
毒理学毒理学毒理学
基因组学就是基因组学.

背景情况:

布苏尔方与环胺 (BuCy) 结合是一种用于血造干细胞移植的标准调节方案.
BuCy会导致严重的性腺毒性,导致近一半男性患者出现不可逆转的不孕症.
现有的小鼠模型通常仅使用busulfan,不能完全复制临床BuCy治疗及其对男性生育能力的影响.

研究的目的:

在小鼠中经过临床相关的BuCy治疗方案后,纵向描述丸损伤和恢复动态.
通过单细胞RNA测序 (scRNA-seq) 调查潜在的BuCy诱导的丸损伤和部分恢复的细胞和分子机制.

主要方法:

给一只小鼠模型给药一个布苏尔和环胺 (BuCy) 方案.
丸组织病理学,精子数和运动性的纵向评估.
单细胞RNA测序 (scRNA-seq) 用于在多个时间点分析生殖细胞群和基因表达变化.

主要成果:

在小鼠中,BuCy治疗引发了显著的丸缩,破坏了胚胎管结构,并减少了精子数和运动能力.
scRNA-seq揭示了生殖细胞的逐渐丧失,在精子干细胞 (SSC) 之前,精子干细胞 (spermatogonia) 已经耗尽.
在28日观察到差异表达基因 (DEGs) 的峰值,功能丰富表明精子生成,RNA代谢和染色质调节的中断.

结论:

这项研究提供了一个全面的,多个时间点的BuCy诱导的丸损伤和恢复在小鼠模型的表征.
这些发现突出了生殖细胞损失的独特细胞动态,并确定了受BuCy治疗影响的关键分子通路.
这项研究为化学疗法诱导的男性不孕症的机制以及治疗干预的潜在途径提供了宝贵的见解.

关键词:

布苏尔夫人布苏尔夫人布苏尔夫人环酸胺的使用方法男性生殖毒性有毒性再生再生再生的过程精子发生是精子生成.丸缩症丸缩症 testicular atrophy testicular atrophy testicular atrophy testicular atrophy testicular atrophy testicular atrophy testicular atrophy testicular atrophy testicular atrophy testicular atrophy testicular atrophy

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