Transition of prenatal prospermatogonia to postnatal spermatogonia

In the mouse, the prospermatogonial phase of male germline development begins during the fetal stages and extends into the neonatal stages when the initial development of spermatogonia then occurs. In the immature testis, undifferentiated spermatogonia are heterogeneous with at least three distinct subpopulations—those spermatogonia that do not self-renew and give rise directly and only to the first spermatogenic wave, those spermatogonia that form spermatogonial stem cells (SSCs) that are capable of undergoing either self-renewal or differentiation such that they can sustain steady-state spermatogenesis throughout the reproductive lifespan of the male, and those spermatogonia that will undergo cell death. The mechanism that regulates which of these fates will be adopted by each developing spermatogonium remains unresolved. However, there is growing evidence that those prospermatogonia that ultimately give rise to SSCs may become predetermined to this fate during the early fetal stages of male germline development, such that these cells follow a unique developmental program that promotes accumulation of characteristics that are particularly advantageous to SSCs. This notion is supported by studies of the maintenance of genetic integrity in developing prospermatogonia and early undifferentiated spermatogonia that do or do not give rise to SSCs.