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Single-cell atlas of human developing and azoospermia patients' testicles reveals the roadmap and defects in somatic microenvironment

By LiangYu Zhao, ChenCheng Yao, XiaoYu Xing, Tao Jing, Peng Li, ZiJue Zhu, Chao Yang, Jing Zhai, RuHui Tian, HuiXing Chen, JiaQiang Luo, NaChuan Liu, ZhiWen Deng, XiaoHan Lin, Na Li, Jing Fang, Jie Sun, ChenChen Wang, Zhi Zhou, Zheng Li

Posted 08 May 2020
bioRxiv DOI: 10.1101/2020.05.07.082024

Non-obstructive azoospermia (NOA) affects 1% of men. However, the unknowns of NOA pathogenesis and even normal spermatogenic microenvironment establishment severely limit the clinical efficacy of NOA treatment. We profiled > 80,000 human testicular single-cell transcriptomes from 10 healthy donors spanning the range from infant to adult and 7 NOA patients. Sertoli cells, which form the scaffold in the testicular microenvironment, exhibited the most obvious damages in NOA patients. We identified the roadmap of Sertoli cell maturation. Notably, Sertoli cells of patients with congenital causes (Klinefelter syndrome and Y chromosome microdeletions) are mature but with abnormal immune response, while the cells in idiopathic NOA (iNOA) are basically physiologically immature. Furthermore, inhibition of Wnt signaling promotes the maturation of Sertoli cells from iNOA patients, allowing these cells to regain their ability to support germ cell survival. We provide a novel perspective on the development of diagnostic methods and therapeutic targets for NOA. ### Competing Interest Statement The authors have declared no competing interest.

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