Morphometric Description of Spermatogonial Stem Cells and Expansion of Their Clonal Derivatives - Male Germline Stem Cells Developmental and Regenerative Potential - page 102

have an inhibiting effect on the proliferation of earlier spermatogonial cell types.
A corollary of this is that, apparently, the lengthy period of quiescence of the A al
spermatogonia that normally lasts from about stage II up until stage VII/VIII is not
required for a proper differentiation of these cells into A1 spermatogonia.
The next question then is, how are the A1 spermatogonia in stage VIII and the
A s,pr,al spermatogonia around stage X stimulated to proliferate again? The prolifera-
tive activity of spermatogonia being inhibited by the density of these cells, the most
obvious reason for a resumption of spermatogonial proliferation would be a
decrease in spermatogonial density. Two events may be of importance here. First,
in stage VI the B spermatogonia give rise to the preleptotene spermatocytes and
possibly these cells no longer inhibit spermatogonial proliferation. In stage VIII,
spermatocytes enter premeiotic S phase and thereafter meiotic prophase. However,
as at about the same time the A1 spermatogonia also enter S phase, these events are
too late for being the stimulus for A1 proliferation. Also, all of these events are too
early to constitute the stimulus for the proliferation of the A s,pr,al spermatogonia.
Second, in stage VIII the A1 spermatogonia that previously were chains of A al
spermatogonia, lying relatively close together in or near the SSC niche, move out
of the niches to the space left by the leptotene spermatocytes that moved to the
adluminal compartment (Yoshida et al. 2007 ). The departure of the A1 spermatogonia
may lower the spermatogonial density in the niches; because of this, A s,pr,al sper-
matogonia are no longer inhibited to proliferate and start to do so from about stage
X onwards. Clearly, these speculations will need further studies.

4.10 Regulation of Spermatogonial Numbers

A final question is whether or not there are regulatory mechanisms that ensure a
more or less constant production of spermatogonia and spermatocytes throughout
the seminiferous epithelium. To answer this question, first the A s,pr,al clonal content
has been determined in a number of large areas of tubule basal membrane of the
Chinese hamster (de Rooij and Janssen 1987 ). Surprisingly, there are large differences
in the density of these cells between different areas. When a regulatory mechanism
exists to ensure an even production of A1 spermatogonia in all areas it will try to
increase the numbers of A s,pr,al spermatogonia in areas where their density is low.
The way to do that is to increase the numbers of stem cells in these areas. However,
the ratios between the numbers of A s spermatogonia and the numbers of clones of
A pr,al spermatogonia in high and in low density areas are not significantly different.
Apparently, the chance of self-renewal of A s spermatogonia remains similar
whether they are surrounded by high numbers of clones of A s,pr,al spermatogonia or
not. As a result, in some areas very low numbers of A1 spermatogonia and in others
very many are formed. Up to fivefold differences have been found (de Rooij and
Janssen 1987 ).
Despite the large differences in the numbers of A1 spermatogonia in different
areas, the numbers of In and B spermatogonia and preleptotene spermatocytes are