Jiang Zesong, Zhang Junwen, Qiu Zhongjian, Zhang Yufei, Li Nan, Hu Jianmeng, Zhu Zhiguo
School of Clinical Medicine, Jining Medical University, Jining, Shandong, China.
Department of Urology, Affiliated Hospital of Jining Medical University, Jining, Shandong, China.
Front Endocrinol (Lausanne). 2025 Mar 19;16:1539063. doi: 10.3389/fendo.2025.1539063. eCollection 2025.
Non-obstructive azoospermia (NOA) constitutes one of the most severe forms of male infertility. Recent advancements in single-cell sequencing have significantly contributed to understanding the molecular landscape of NOA in human testicular tissues, elucidating the factors that underpin spermatogenic dysfunction. This technology has improved our understanding of the condition at a cellular level. Concurrently, bioinformatics developments have facilitated the re-analysis of publicly available single-cell datasets, offering novel insights into the disorder. Nevertheless, a comprehensive review integrating primary and re-analysis studies of single-cell sequencing in NOA is lacking. This review systematically evaluates 10 primary studies reporting original single-cell sequencing data of human NOA testicular samples and 22 secondary studies that re-analyzed these published data. We explore single-cell sequencing applications in germ cells, Sertoli cells, and Leydig cells, offering a comprehensive overview of molecular insights into spermatogenic dysfunction. Our review highlights novel findings in secondary studies, including the roles of transcriptional regulators, RNA transcription, endocrine disruptors, and microtubular cytoskeleton, thereby bridging primary studies and re-analysis studies. Additionally, we discussed future research directions and the challenges of translating single-cell research findings into clinical applications. In summary, single-cell sequencing offers a high-resolution, single-cell perspective of NOA testicular tissue, paving the way for innovative therapeutic strategies in male infertility.
非梗阻性无精子症（NOA）是男性不育最严重的形式之一。单细胞测序的最新进展极大地有助于了解人类睾丸组织中NOA的分子格局，阐明导致生精功能障碍的因素。这项技术在细胞水平上增进了我们对该病症的理解。与此同时，生物信息学的发展促进了对公开可用的单细胞数据集的重新分析，为该疾病提供了新的见解。然而，缺乏对NOA单细胞测序的原始研究和重新分析研究进行整合的全面综述。本综述系统地评估了10项报告人类NOA睾丸样本原始单细胞测序数据的原始研究以及22项重新分析这些已发表数据的二次研究。我们探讨了单细胞测序在生殖细胞、支持细胞和间质细胞中的应用，全面概述了对生精功能障碍的分子见解。我们的综述突出了二次研究中的新发现，包括转录调节因子、RNA转录、内分泌干扰物和微管细胞骨架的作用，从而架起了原始研究和重新分析研究之间的桥梁。此外，我们讨论了未来的研究方向以及将单细胞研究结果转化为临床应用的挑战。总之，单细胞测序为NOA睾丸组织提供了高分辨率的单细胞视角，为男性不育的创新治疗策略铺平了道路。
