Morphometric Description of Spermatogonial Stem Cells and Expansion of Their Clonal Derivatives - Male Germline Stem Cells Developmental and Regenerative Potential - page 90

4.1 Outline

This review first deals with the various types of spermatogonia that can be
distinguished and the scheme of spermatogonial multiplication and stem cell
renewal in rodents and the ram, in which this process has been studied in most
detail. Then the morphological characteristics of the spermatogonial cell types are
described, including their presence and behavior during the epithelial cycle and
how these cells can best be studied at the cellular level. In the next section, the
numbers of the A s, pr, al spermatogonia during the course of the epithelial cycle and
the number of stem cells per testis are discussed. Subsequently, the extensive cell-
kinetic studies using 3 H-thymidine in the rat and Chinese hamster are summarized.
Detailed data on the cell cycle characteristics of all types of spermatogonia in these
species are known. The spermatogonial stem cells that are supposed to be single
cells are discussed. However, theoretical and experimental considerations seem to
indicate that some of the pairs may still have stem cell properties that can split in
singles or new pairs again at division. Next, the proliferative activity of the A s, pr, al
spermatogonia during the course of the epithelial cycle is described, as well as the
growth fraction data that can be calculated for the various cell types. The duration
of the period of high proliferative activity of the A s, pr, al spermatogonia during the
epithelial cycle depends on the numbers of differentiating type of spermatogonia
present, in a kind of a feedback regulation loop. This regulation on the cellular
level is also described. The final section describes how the density of germ cells
is regulated by apoptosis of the surplus of A1-A4 spermatogonia produced by the
A s, pr, al spermatogonia.

4.2 Introduction

Up until about 1994, when the spermatogonial stem cell (SSC) transplantation
assay was published (Brinster and Avarbock 1994 ; Brinster and Zimmermann
1994 ), most research on spermatogonia was carried out at the cellular level in testis
sections and whole mounts of seminiferous tubules. Studies on SSCs could not be
conducted otherwise than by way of cell counts and labeling experiments and by
studying recovery after cell loss. Now virtually all research on SSCs and its direct
progeny is carried out in vitro and on populations of SSCs purified directly or indi-
rectly, using membrane markers for SSCs, under the guidance of the transplantation
assay. A host of factors have now been detected that play a role in regulating SSC
behavior and spermatogonial differentiation (Oatley and Brinster 2008 ; Aponte
et al. 2005 ). Now the new data, largely obtained in vitro , can be compared with the
old knowledge obtained at the cellular level in testis tissue. To facilitate this
comparison this review summarizes the morphological and morphometrical data
obtained before the molecular and culture era, starting at about 1994. After all, the
final goal still is to understand the regulation of the spermatogonial compartment
in the normal in vivo situation.