Unveiling the spermatogonial stem cell niche in primates: a histological approach

The maintenance of seminiferous epithelium function depends on the intricate molecular and cellular interactions between spermatogonial stem cells (SSCs) and their cognate niche. To sustain continuous sperm production, a delicate balance must be maintained among various niche factors that regulate SSC fate decisions by promoting either self-renewal or spermatogenic commitment of undifferentiated spermatogonia (undiff-SPG). Despite its critical importance, our understanding of SSC homeostasis remains limited, particularly concerning the spatial distribution of SSCs within the testicular microenvironment. In this study, we aim to characterize the SSC niche and its regulation in primates by identifying novel putative cell-cell interactions between somatic cells and SSCs and by evaluating the histological distribution of different spermatogonia subpopulations throughout the seminiferous epithelium cycle. The analysis of protein expression of the published L-R (Ligand-Receptor) pairs we selected (BMP4-BMPR1B and WNT5A-RYK) revealed that only the BMP4-BMPR1B pair showed a positive correlation between RNA and protein expression in both human and monkey testis. Remarkably, the spatial organization of different SPG subsets appears to be coordinated with the stages of the seminiferous epithelium cycle (SEC), suggesting dynamic regulation of SSC behavior throughout sperm production. Our study contributes to the growing body of literature aimed at deciphering the complexities of SSC biology and the regulation of spermatogenesis in mammalian species, with implications for understanding male fertility