Spermatogonial stem cell functions in physiological and pathological conditions.

Sperm have a vital role in the continuity of a species by contributing genetic information to the next generation. Production of these specialized gametes in numbers sufficient to confer normal fertility occurs via cycling of the spermatogenic lineage, a process referred to as spermatogenesis. Continuity relies on the activities of a self-renewing reservoir of spermatogonial stem cells (SSCs) from which progenitors will arise that transiently amplify in number before committing to a pathway of terminal differentiation. A primary population of SSCs is established during neonatal development from a pool of quiescent gonocyte precursors that forms in embryogenesis. Disruption of this process has dire consequences on maintenance of a cycling spermatogenic lineage in adulthood. At present, the molecular mechanisms underlying initial formation of the SSC pool are largely undefined. However, several transcription factors and posttranscriptional regulators have been identified as important regulators of SSC self-renewal from studies with mutant mouse models and experimental manipulation within primary cultures of mouse SSCs. Importantly, loss of function of these self-renewal factors may be underlying causes of infertility. Furthermore, disruption in the establishment of the SSC state within gonocytes or misregulation of self-renewal may manifest as testicular germ cell tumors in postnatal life.