Morphometric Description of Spermatogonial Stem Cells and Expansion of Their Clonal Derivatives - Male Germline Stem Cells Developmental and Regenerative Potential - page 103

similar everywhere, in tubules in the appropriate stages (de Rooij and Lok 1987 ).
Hence, in between A1 spermatogonia in stage VIII and In spermatogonia in stage
III, the differences in differentiating spermatogonial density are eliminated. As can
be concluded from cell kinetic studies using 3 H-thymidine labeling, at each division
all differentiating spermatogonia go through division (Lok and de Rooij 1983a ).
Therefore, differences in cell density cannot be evened out by letting cells in high
density areas skip a division. The most likely explanation is that in the normal situ-
ation the stem cells always produce too many differentiating spermatogonia and
that the surplus of cells produced is eliminated by way of apoptosis in between A1
and In spermatogonia. In high density areas relatively many A2-A4 spermatogonia
will enter apoptosis and only few when the density is low. In the end, differentiating
spermatogonial density is the same everywhere. Apparently, the well-known phe-
nomenon of spermatogonial apoptosis in the normal testis is just the way germ cell
density is regulated and probably has nothing to do with a selection for the best
germ cells, as has often been suggested.

4.11 Conclusion

The spermatogonial lineage in rodents and rams has been described in great detail
at the morphological level. All subsequent types of germ cells are known, sper-
matogonial numbers have been determined, and their cell cycle behavior has been
documented in detail. Furthermore, a scheme of spermatogonial multiplication and
stem cell renewal has been devised on which most investigators agree, although
some details are still a matter of debate. It remains to be unequivocally clarified
whether or not A pr and A al spermatogonia can still split into A s , A pr , or smaller
chains of A al spermatogonia and whether some sort of de-differentiation can take
place. An interesting point for further studies will be to find the factors responsible
for the inhibition of A s,pr,al spermatogonial proliferation and to see how the various
growth factors found to enhance A s,pr,al spermatogonial proliferation function with
respect to the epithelial cycle. Is there a changing pattern in the secretion of growth
factors by Sertoli cells during the epithelial cycle? It will be a challenging task to
fit in the many data that are presently generated on purified spermatogonia/SSCs
into an understanding of how spermatogonial multiplication and stem cell renewal
is regulated in the normal in vivo situation, which is even more complex because of
the presence of the epithelial cycle, something that cannot be simulated in vitro .

References

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Brinster RL & Avarbock MR 1994 Germline transmission of donor haplotype following
spermatogonial transplantation. Proc. Natl. Acad. Sci. U. S. A. 91 11303-11307.