Essential roles of interstitial cells in testicular development and function.

BACKGROUND: Testicular architecture and sperm production are supported by a complex network of communication between various cell types. These signals ensure fertility by: regulating spermatogonial stem/progenitor cells; promoting steroidogenesis; and driving male-specific differentiation of the gonad. Sertoli cells have long been assumed to be the major cellular player in testis organogenesis and spermatogenesis. However, cells in the interstitial compartment, such as Leydig, vascular, immune, and peritubular cells, also play prominent roles in the testis but are less well understood. OBJECTIVES: Here, we aim to outline our current knowledge of the cellular and molecular mechanisms by which interstitial cell types contribute to spermatogenesis and testicular development, and how these diverse constituents of the testis play essential roles in ensuring male sexual differentiation and fertility. METHODS: We surveyed scientific literature and summarized findings in the field that address how interstitial cells interact with other interstitial cell populations and seminiferous tubules (i.e., Sertoli and germ cells) to support spermatogenesis, male-specific differentiation, and testicular function. These studies focused on 4 major cell types: Leydig cells, vascular cells, immune cells, and peritubular cells. RESULTS AND DISCUSSION: A growing number of studies have demonstrated that interstitial cells play a wide range of functions in the fetal and adult testis. Leydig cells, through secretion of hormones and growth factors, are responsible for steroidogenesis and progression of spermatogenesis. Vascular, immune, and peritubular cells, apart from their traditionally acknowledged physiological roles, have a broader importance than previously appreciated and are emerging as essential players in stem/progenitor cell biology. CONCLUSION: Interstitial cells take part in complex signaling interactions with both interstitial and tubular cell populations, which are required for several biological processes, such as steroidogenesis, Sertoli cell function, spermatogenesis, and immune regulation. These various processes are essential for testicular function and demonstrate how interstitial cells are indispensable for male fertility.

Sox100B, a Drosophila group E Sox-domain gene, is required for somatic testis differentiation.

Sex determination mechanisms are thought to evolve rapidly and show little conservation among different animal species. For example, the critical gene on the Y chromosome, SRY, that determines sex in most mammals, is not found in other animals. However, a related Sox domain transcription factor, SOX9, is also required for testis development in mammals and exhibits male-specific gonad expression in other vertebrate species. Previously, we found that the Drosophila orthologue of SOX9, Sox100B, is expressed male-specifically during gonad development. We now investigate the function of Sox100B and find, strikingly, that Sox100B is essential for testis development in Drosophila. In Sox100B mutants, the adult testis is severely reduced and fails to interact with other parts of the reproductive tract, which are themselves unaffected. While a testis initially forms in Sox100B mutants, it fails to undergo proper morphogenesis during pupal stages, likely due to defects in the pigment cells. In contrast, no substantive defects are observed in ovary development in Sox100B mutant females. Thus, as is observed in mammals, a Sox9 homolog is essential for sex-specific gonad development in Drosophila, suggesting that the molecular mechanisms regulating sexually dimorphic gonad development may be more conserved than previously suspected.