Concise review: Defining characteristics of mammalian spermatogenic stem cells

Abstract

The enormous number of sperms produced daily and over the lifetime of mammals requires a stable source of stem cells that give rise to progenitor cells that proceed through spermatogenesis. Spermatogenic stem cells develop from primitive germ cells that occupy the developing gonad. A transplantation assay was developed for the spermatogenic stem cells, and it remains the only functional measure of authentic stem cells in the testis. Somatic cells comprise a "niche" environment that is essential for the maintenance of stem cell activity. Dividing progenitor cells have intercellular bridges and form syncytia with 2, 4, 8, or 16 cells. Fragmentation of these syncytia may allow some progenitor cells to occupy "niches" and function as stem cells, but this notion requires further investigation. Spermatogenic stem cells can be maintained in culture and are influenced by a number of growth factors. Thus far, the ultimate differentiation of cultured stem cells into functional gametes has not been demonstrated with any efficiency and reproducibility. The ability to maintain spermatogenic stem cells in culture and to induce differentiation into haploid cells and sperm could have many important implications for human medicine.

Fig.1

Outline of the role for spermatogonial stem cells (SSCs) in spermatogenesis. The SSC arises from prospermatogonia (also termed gonocytes) that are derived from primordial germ cells. The SSC is a single A undifferentiated spermatogonium (A_single). Asymmetric division gives rise to both another self-renewing SSC and a progenitor A_single. The progenitor A_single spermatogonium divides to give rise to A_aligned progenitor spermatogonia (syncytia of 2, 4, 8, and up to 16 cells). There is some evidence that fragmentation of these syncytia can lead to conversion to A_single spermatogenic stem cells (A_s-SSC). The A_aligned spermatogonia become A_{differentiating} spermatogonia under the influence of retinoic acid. The differentiating spermatogonia undergo a series of synchronized cell divisions to eventually form spermatocytes.