New insights into male gametogenesis: what about the spermatogonial stem cell niche?

The spermatogonial stem cells (SSCs) are at the foundation of spermatogenesis. They can self-renew and generate a large number of differentiated germ cells. A balance between SSC renewal and differentiation in the adult testis is essential to maintain normal spermatogenesis and fertility. These two processes are tightly regulated by intrinsic gene expression in the stem cells and extrinsic signals, including soluble factors and adhesion molecules from the surrounding microenvironment, known as the SSC niche. Few factors which are only found in germ cells are recognized as indispensable to SSC maintenance or differentiation. Plzf, a transcriptional repressor protein, and TAF-4b, a germ cell specific component of the RNA polymerase complex, are considered to be essential for SSC renewal, whereas the transcription factors Sohlh1 and 2 appear to be crucial for spermatogonial differentiation. By providing glial cell-line-derived neurotrophic factor (GDNF) and stem cell factor (SCF) for SSCs and segregating them, the Sertoli cell is one of the major contributors to stem cell niche regulation Another Sertoli cell product, ERM, a transcription factor which is exclusively expressed in mature Sertoli cells, has been shown to be required for SSC self-renewal and maintenance of spermatogenesis in adult mice. It has been hypothesized that SSC niche regulation changes with age. SSC self-renewal could be controlled by GDNF during the perinatal period of development while it is dependent on ERM, during the pubertal period.