HnRNPK is essential for Sertoli cells development and male fertility in mice

Abstract

Abstract Background: Sertoli cells (SCs), a type of somatic supporting cells situated within the spermatogenic niche, play a crucial role in the maturation of germ cells. Nevertheless, the precise mechanisms governing the development of SCs and their impact on spermatogenesis remain incompletely understood. Results: In this study, we have identified hnRNPK, a multifunctional protein involved in signal transduction and gene expression regulation, as a significant novel regulatory factor in the development of neonatal SCs and pre-pubertal testicular growth in mice. In order to gain a deeper understanding of the roles played by hnRNPK in spermatogenesis, we conducted a thorough investigation utilizing SCs specific Hnrnpk knockout mice, which were obtained through the crossing of Hnrnpkflox/flox mice with Amh-Cre mice. The findings demonstrated that the absence of Hnrnpk in SCs had a significant impact on various aspects, including the proliferation and localization of SCs, the organization of seminiferous tubules, the occurrence of apoptotic cell death in both SCs and germ cells within the tubules, as well as the reduction in testis size and overall fecundity. Through the integration of RNA-seq and bioinformatics analysis, our study has unveiled the dysregulation of the transcriptome-wide expression of crucial genes involved in the control of SCs and germ cells fate. These genes encompass various processes, including cell-cell adhesion, cell proliferation and migration, piRNA processing, SC differentiation, and secretion. Conclusions: Our findings highlight the indispensable role of hnRNPK in SCs for the development of the testis and also shed light on a previously unknown function of hnRNPK in male germ cell survival and differentiation, specifically by modulating cell-cell communication.