Spermatogonial Stem Cells

Spermatogenesis is a continuous, highly organized process comprised of sequential steps of cell proliferation and differentiation ( 1 ). In male mammals, spermatogenesis proceeds for the reproductive lifetime of the animals. The continuation of this process depends on a pool of spermatogonial stem cells within the testes that undergo asymmetric division to both maintain the stem cell population and give rise to progenitors that will proceed through spermatogenesis to generate mature spermatozoa ( see Fig. 1A ). The male germline proceeds through several developmental steps prior to the establishment and initiation of spermatogonial stem cell division in the testis ( 2 – 4 ). Primordial germ cells (PGCs) are the founders of the gametes. Progenitors in mice have been recognized in the proximal epiblast ( 5 ). The PGCs proliferate and migrate from their site of origin to the future position of the gonad, where they associate with somatic gonadal precursor cells to form the gonad ( 5 ). Once within the gonad, the PGCs differentiate in a sex-specific manner, including a distinct program of proliferation and quiescence ( see Fig. 1A ) ( 5 ). In the male genital ridge, the PGCs become enclosed by somatic supporting cells, the precursor Sertoli cells. PGCs and Sertoli cells then, together, form solid strands of cells, which are called seminiferous cords. Later during development, these cords form a lumen and become seminiferous tubules. When the PGCs are enclosed in seminiferous cords, they change morphologically and are then called gonocytes.   Fig. 1A.  ( A ) Origin of spermatogonial stem cells in prenatal and newborn mice.