Remodeling of the postnatal mouse testis is accompanied by dramatic changes in stem cell number and niche accessibility

Little is known about stem cell biology or the specialized environments or niches believed to control stem cell renewal and differentiation in self-re newing tissues of the body. Functional assays for stem cells are available only for hematopoiesis and spermatogenesis, and the microenvironment or nic he, for hematopoiesis is relatively inaccessible, making it difficult to an alyze donor stem cell colonization events in recipients. In contrast, the r ecently developed spermatogonial stem cell assay system allows quantitation of individual colonization events, facilitating studies of stem cells and their associated microenvironment. By using this assay system, we found a 3 9-fold increase in male germ-line stem cells during development from birth to adult in the mouse. However, colony size or area of spermatogenesis gene rated by neonate and adult stem cells, 2-3 months after transplantation int o adult tubules, was similar (similar to0.5 mm(2)). In contrast, the microe nvironment in the immature pup testis was 9.4 times better than adult testi s in allowing colonization events, and the area colonized per donor stem ce ll, whether from adult or pup, was about 4.0 times larger in recipient pups than adults. These factors facilitated the restoration of fertility by don or stem cells transplanted to infertile pups. Thus, our results demonstrate that stem cells and their niches undergo dramatic changes in the postnatal testis, and the microenvironment of the pup testis provides a more hospita ble environment for transplantation of male germ-line stem cells.