Abstract
Spermatogenesis is a complex and dynamic process which is precisely controlledby genetic and epigenetic factors. With the development of new technologies (e.g., single-cell RNA sequencing), increasingly more regulatory genes related to spermatogenesis have been identified. In this review, we address the roles and mechanisms of novel genes in regulating the normal and abnormal spermatogenesis. Specifically, we discussed the functions and signaling pathways of key new genes in mediating the proliferation, differentiation, and apoptosis of rodent and human spermatogonial stem cells (SSCs), as well as in controlling the meiosis of spermatocytes and other germ cells. Additionally, we summarized the gene regulation in the abnormal testicular microenvironment or the niche by Sertoli cells, peritubular myoid cells, and Leydig cells. Finally, we pointed out the future directions for investigating the molecular mechanisms underlying human spermatogenesis. This review could offer novel insights into genetic regulation in the normal and abnormal spermatogenesis, and it provides new molecular targets for gene therapy of male infertility.
Highlights
Received: 3 February 2021Accepted: 11 March 2021Published: 17 March 2021Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.Spermatogenesis is an elaborately organized process inwhich diploid spermatogonial stem cells (SSCs) differentiate into spermatocytes and haploid spermatozoa
Wildtype mouse SSCs survive, but their proliferation ability is abolished due to the reduction of ID4 expression. These results indicate that ID4 is a marker of male germline stem cells and it is critical for the regulation of cellself-renewal [25]
FGF9 promotes mouse SSC proliferation by p38 MAPK signaling [34], while we have found that VEGFC/VEGFR3 signaling regulates mouse SSCproliferation via the activation of AKT/MAPK and Cyclin D1 pathway and mediates the apoptosis by affecting
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Spermatogenesis is an elaborately organized process inwhich diploid spermatogonial stem cells (SSCs) differentiate into spermatocytes and haploid spermatozoa. This process is collaborated by somatic cells in the testis, including Sertoli cells, peritubular myoid cells, and Leydig cells. We and others have revealed the molecular mechanisms underlying rodent spermatogenesis. Several new technologies, e.g., single-cell RNA sequencing and RNA deep sequencing, have been developed, making it feasible to identify more and more novel genes that are involved in the regulation of rodent and human spermatogenesis. We addressed the functions and mechanisms of key novel genes in controlling the mitosis and meiosis of rodent and human male germ cells.
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