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

Abstract

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.

Investigating the role of a testis-expressed gene Tex2 in spermatogenesis in mice

“…Among these genes, 47 have been developed as mouse models, predominantly as knockout models [14]. Notably, knockout mice of Tex20, Tex23, Tex169, Tex189, and Tex292 were found to be embryonic lethal; the fertility of Tex22, Tex33, Tex35, Tex36, Tex37, and Tex271 knockout males remained unaffected; Tex17, Tex18, and Tex40 knockout mice displayed reduced fertility; whereas Tex11, Tex12, Tex14, Tex15, Tex19, Tex38, and Tex101 knockout mice exhibited sterile phenotypes [15][16][17][18][19]. Moreover, the functions of the remaining TEX members and their impact on fertility in mice are yet to be fully elucidated.…”