The involvement of bioactive factors in the self-renewal and stemness maintenance of spermatogonial stem cells

Spermatogenesis is usually accompanied throughout mammalian lifetime, transmitting genetic information to the next generation, which is mainly dependent on the self-renewal and differentiation of spermatogonial stem cells (SSCs). With further investigation on profiles of SSCs, the previous prevailing orthodoxy that SSCs are unipotent stem cells to differentiate into spermatids only, has been challenged. More notably, accumulating evidence has demonstrated that SSCs are capable of giving rise to cell lineages of the three germ layers, highlighting potential important applications of SSCs for regenerative medicine. Nevertheless, it is unknown how the proliferation and stemness maintenance of SSCs are regulated intrinsically and strictly controlled in a special niche microenvironment in the seminiferous tubules. Based on the special niche microenvironment for SSCs, it is of vital interest to summarize the recent knowledge regarding several critical bioactive molecules in the self-renewal and stemness maintenance of SSCs. In this review, we discuss most recent findings about these critical bioactive factors and further address the new advances on the self-renewal and stemness maintenance of SSCs.