Decoding the pathogenesis of spermatogenic failure in cryptorchidism through single-cell transcriptomic profiling

作者：Xiaoyan Wang, Qiang Liu, Ziyan Zhuang, Jianxing Cheng, Wenxiu Zhang, Qiaoling Jiang, Yifei Guo, Ran Li, Xiaojian Lu, Lina Cui, Jiaming Weng, Yanlin Tang, Jingwei Yue, Songzhan Gao, Kai Hong, Jie Qiao, Hui Jiang, Jingtao Guo, Zhe Zhang · 发表于：Cell Reports Medicine · 年份：2024 · DOI：10.1016/j.xcrm.2024.101709 · 被引用次数：13 · 研究领域：Sperm and Testicular Function、Reproductive System and Pregnancy、Reproductive Biology and Fertility

Cryptorchidism, commonly known as undescended testis, affects 1%–9% of male newborns, posing infertility and testis tumor risks. Despite its prevalence, the detailed pathophysiology underlying male infertility within cryptorchidism remains unclear. Here, we profile and analyze 46,644 single-cell transcriptomes from individual testicular cells obtained from adult males diagnosed with cryptorchidism and healthy controls. Spermatogenesis compromise in cryptorchidism links primarily to spermatogonium self-renewal and differentiation dysfunctions. We illuminate the involvement of testicular somatic cells, including immune cells, thereby unveiling the activation and degranulation of mast cells in cryptorchidism. Mast cells are identified as contributors to interstitial fibrosis via transforming growth factor β1 (TGF-β1) and cathepsin G secretion. Furthermore, significantly increased levels of secretory proteins indicate mast cell activation and testicular fibrosis in the seminal plasma of individuals with cryptorchidism compared to controls. These insights serve as valuable translational references, enriching our comprehension of testicular pathogenesis and informing more precise diagnosis and targeted therapeutic strategies for cryptorchidism. • Cryptorchidism in men compromises spermatogenesis due to spermatogonial dysfunction • Cryptorchidism results in mast cell activation and degranulation • Mast cells and elevated levels of TGF-β1 proteins are linked to testicular fibrosis • ...