Germline stem cell transplantation and transgenesis

Abstract

The recently developed testis cell transplantation method provides a powerful approach to studying the biology of the male germline stem cell and its microenvironment, the stem cell niche. The technique also is being used to examine spermatogenic defects, correct male infertility, and generate transgenic animals.

Fig. 1

Testis cell transplantation method. A single-cell suspension is produced from a fertile donor testis (A). The cells can be cultured (B) or microinjected into the lumen of seminiferous tubules of an infertile recipient mouse (C). Only a spermatogonial stem cell can generate a colony of spermatogenesis in the recipient testis. When testis cells carry a reporter transgene that allows the cells to be stained blue, colonies of donor cell–derived spermatogenesis are identified easily in recipient testes as blue stretches of tubule (D). Mating the recipient male to a wild-type female (E) produces progeny (F), which carry donor genes. Genetic modification can be introduced while the stem cells are in culture.

Fig. 2

Organization of germ cells and somatic cells in a seminiferous tubule. Germ cell differentiation proceeds through multiple stages, including spermatogonia (gonia), spermatocyte (cyte), spermatid (tid), and finally spermatozoa, which are released into the lumen. Sertoli cells are joined continuously around the tubule by tight junctions (denoted by the arrowheads) that regulate passage of cells and large molecules between the basal compartment, containing spermatogonia, and the luminal compartment, containing differentiating germ cells. Only a small fraction (~1%) of spermatogonia are stem cells; the remainder have begun differentiating. [Adapted with permission from (28)]