Wu Xiaolong, Liu Hanchao, Hua Lin, Gao Xintao, Hu Longfei, Wang Lingling, Bu Tiao, Sun Fei, Yan Cheng C
Department of Urology and Andrology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Singleron Biotechnologies Ltd., Nanjing, Jiangsu, China.
Adv Exp Med Biol. 2025;1469:173-205. doi: 10.1007/978-3-031-82990-1_9.
This study employs single-cell RNA sequencing (scRNA-seq) to investigate human spermatogenesis across developmental stages and under pathological conditions, including non-obstructive azoospermia (NOA). The analysis highlights the critical role of Sertoli cells in supporting germ cell development by providing structural support, paracrine factors, and essential nutrients. Pathological conditions, such as NOA and Klinefelter syndrome, reveal significant disruptions in Sertoli cell function, including impaired cell signaling, mitochondrial activity, and transcriptional regulation. These changes are closely linked to defects in germ cell progression and spermatogenic failure. Comparative profiling also identifies stage-specific transcriptional changes in both Sertoli and Leydig cells, uncovering their dynamic interactions with germ cells. This work provides new insights into the cellular and molecular mechanisms of spermatogenesis and identifies potential biomarkers and therapeutic targets, particularly emphasizing the pivotal contributions of Sertoli cells in maintaining testicular homeostasis and fertility.
本研究采用单细胞RNA测序（scRNA-seq）来研究人类在不同发育阶段以及包括非梗阻性无精子症（NOA）在内的病理条件下的精子发生过程。分析突出了支持细胞在通过提供结构支持、旁分泌因子和必需营养物质来支持生殖细胞发育方面的关键作用。诸如NOA和克兰费尔特综合征等病理状况揭示了支持细胞功能的显著破坏，包括细胞信号传导、线粒体活性和转录调控受损。这些变化与生殖细胞进展缺陷和生精失败密切相关。比较分析还确定了支持细胞和间质细胞中特定阶段的转录变化，揭示了它们与生殖细胞的动态相互作用。这项工作为精子发生的细胞和分子机制提供了新的见解，并确定了潜在的生物标志物和治疗靶点，特别强调了支持细胞在维持睾丸内环境稳定和生育能力方面的关键作用。
