Deciphering the Molecular Characteristics of Human Idiopathic Nonobstructive Azoospermia from the Perspective of Germ Cells

• Published in: Advanced science Vol. 10; no. 17; pp. e2206852 - n/a
• Main Authors: Chen, Yidong, Liu, Xixi, Zhang, Li, Zhu, Feiyin, Yan, Liying, Tang, Wenhao, Zhang, Zhe, Liu, Qiang, Jiang, Hui, Qiao, Jie
• Format: Journal Article
• Language: English
• Published: Germany John Wiley & Sons, Inc 01.06.2023; John Wiley and Sons Inc; Wiley
• Subjects: Apoptosis; Azoospermia - genetics; Azoospermia - metabolism; Azoospermia - pathology; Cell cycle; Chromosomes; clinical diagnosis; Gene expression; Germ Cells; Humans; Infertility; Infertility, Male - pathology; Male; molecular characteristics; nonobstructive azoospermia; Pathogenesis; Sperm; Spermatogenesis; spermatogenic capacity predictor; Stem cells; Testis - metabolism; Testis - pathology; clinical diagnosis; pathogenesis; spermatogenic capacity predictor; germ cells; nonobstructive azoospermia; molecular characteristics
• ISSN: 2198-3844; 2198-3844
• DOI: 10.1002/advs.202206852

Nonobstructive azoospermia (NOA) is one of the most important causes of male infertility, accounting for 10–15% of infertile men worldwide. Among these, more than 70% of cases are idiopathic NOA (iNOA), whose pathogenesis and molecular basis remain unknown. This work profiles 3696 human testicular single‐cell transcriptomes from 17 iNOA patients, which are classified into four classes with different arrest periods and variable cell proportions based on the gene expression patterns and pathological features. Genes related to the cell cycle, energy production, and gamete generation show obvious abnormalities in iNOA germ cells. This work identifies several candidate causal genes for iNOA, including CD164, LELP1, and TEX38, which are significantly downregulated in iNOA germ cells. Notably, CD164 knockdown promotes apoptosis in spermatogonia. Cellular communications between spermatogonial stem cells and Sertoli cells are disturbed in iNOA patients. Moreover, BOD1L2, C1orf194, and KRTCAP2 are found to indicate testicular spermatogenic capacity in a variety of testicular diseases, such as Y‐chromosome microdeletions and Klinefelter syndrome. In general, this study analyzes the pathogenesis of iNOA from the perspective of germ cell development, transcription factor (TF) regulatory networks, as well as germ cell and somatic cell interactions, which provides new ideas for clinical diagnosis. Based on the gene expression patterns and pathological features, idiopathic nonobstructive azoospermia (NOA) patients are classified into four classes. Transcriptional patterns are altered in idiopathic NOA patients, especially in cell cycle activity, energy production, and cellular communications between germ cells and somatic cells. A set of predictive genes is identified to indicate testicular spermatogenic capacity, which may be helpful for clinical diagnosis.