Zhou Liwei, Liu Hanchao, Chen Yuming, Hua Lin, Wu Xiaolong, Gao Xintao, Mao Le
Department of Urology, Xinghua People's Hospital Affiliated to Yangzhou University, Taizhou 225700, Jiangsu, China.
Department of Urology and Andrology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, Zhejiang, China.
Reprod Biol. 2025 Mar;25(1):100972. doi: 10.1016/j.repbio.2024.100972. Epub 2024 Nov 19.
Male infertility and impaired spermatogenesis are significant concerns in reproductive health, often linked to disruptions in the cellular and molecular processes within the testis. The cellular composition and transcriptional dynamics of human testicular tissue are crucial for understanding these issues. Previous studies have largely relied on bulk tissue analysis, which obscures the distinct roles and interactions of specific cell types. Here, through a comprehensive single-cell transcriptomic analysis of human testes across various developmental stages and pathological conditions, we reveal the intricate cellular heterogeneity and the molecular mechanisms underlying testicular function. Our study identifies significant disruptions in the differentiation trajectories of Germ cells in conditions such as Klinefelter syndrome (KS), AZFa deletion, and Sertoli-cell-only syndrome (SCOS). We further uncover key transcription factors and regulatory networks governing Leydig cell function, particularly those related to steroidogenesis and hormonal regulation. These findings highlight the organized yet complex cellular and molecular landscape of the testis and uncover critical pathways altered in male infertility. Collectively, our data suggest that targeted therapeutic strategies could be developed to address specific disruptions in testicular cell populations and their associated regulatory networks.
男性不育和精子发生受损是生殖健康中的重大问题，通常与睾丸内细胞和分子过程的紊乱有关。人类睾丸组织的细胞组成和转录动态对于理解这些问题至关重要。以往的研究主要依赖于整体组织分析，这掩盖了特定细胞类型的独特作用和相互作用。在这里，通过对不同发育阶段和病理状况的人类睾丸进行全面的单细胞转录组分析，我们揭示了复杂的细胞异质性以及睾丸功能的分子机制。我们的研究确定了在克氏综合征（KS）、AZFa缺失和唯支持细胞综合征（SCOS）等情况下生殖细胞分化轨迹的显著破坏。我们进一步发现了调控睾丸间质细胞功能的关键转录因子和调控网络，特别是那些与类固醇生成和激素调节相关的因子和网络。这些发现突出了睾丸有组织但复杂的细胞和分子格局，并揭示了男性不育中改变的关键途径。总体而言，我们的数据表明，可以制定针对性的治疗策略来解决睾丸细胞群体及其相关调控网络中的特定破坏。
