Spermatogonial stem cells (SSCs; A(s) spermatogonia) and their direct descendants (A(pr) and A(al) spermatogonia) are preferentially located in those areas of the seminiferous tubules that border on the interstitial tissue. Fewer of these cells are present in tubule areas directly bordering on another tubule. Therefore, the SSC niche is related to the presence of interstitial tissue. The somatic cells within the seminiferous tubules, the Sertoli cells, are able to produce growth factors that stimulate self-renewal (GDNF, FGF2) and differentiation (activin A, BMP4, and SCF) of the SSCs. As Sertoli cells are everywhere on the basal membrane of the tubules, other factors coming from outside the tubules must determine, either directly or indirectly via Sertoli cells, whether in a particular area self-renewal of SSCs will be preferred or differentiation in the form of A(pr) formation. Self-renewal will be preferred in the stem cell niche and differentiation outside of the niche. Factors that could link the niche to the interstitial tissue are CSF1, produced by Leydig cells that stimulate stem cell proliferation and FSH, the concentration of which will be highest near blood vessels and that stimulates GDNF production by Sertoli cells.