Questions about spermatogonia posed and answered since 2000.

This review focuses on 3 important advances in our understanding of rodent spermatogonial stem cells (SSC) that have emerged since 2000: the identity of SSC, the existence of a SSC niche, and gene expression in spermatogonia. It is now apparent that the original scheme, in which the A(single) (A(s)) spermatogonia are the only stem cells, may be too simple. Rather, separation of pairs of A(paired) (A(pr)) spermatogonia into singles might also play a role in the steady state situation. However, evidence that in the normal epithelium fragmentation of chains of A(aligned) (A(al)) spermatogonia into smaller clones also plays a role is not yet conclusive. New evidence presented during the last decade indicates that the A(s),A(pr), and A(al) (A(s,pr,al)) spermatogonia are not localized at random over the tubule basal lamina, as originally assumed, but are restricted to those areas that border on interstitial tissue and, in particular, to areas containing venules and arterioles, suggesting a specific relationship of this localization with a possible SSC niche. Finally, gene expression studies are showing how both extrinsic factors produced by Sertoli cells and intrinsic factors that are products of the germ cells act either to maintain progenitor cells or to promote differentiation and the commitment to meiosis. Taken together, this new knowledge adds to our understanding of the balance between 2 opposing forces: one promoting the undifferentiated state and the other promoting the commitment to meiosis and differentiation that is essential for spermatogenesis to proceed.