Biomedical Engineering Reference
In-Depth Information
more slowly than differentiating cells. Huckins carried out an autoradiographic
study on whole mounts of seminiferous tubules of rats that were given
3
H-thymidine
and studied the presence of labeled spermatogonia at longer times after injection
(Huckins
1971b
). She reported the existence of LRCs and proposed that the LRCs,
a subpopulation of the A
s
spermatogonia, were the real stem cells and that the
short-cycling A
s
spermatogonia were inclined to differentiate. However, Lok et al.
carried out a comparable but more extensive study in the Chinese hamster and did
not find evidence for the presence of LRCs in this species (Lok et al.
1984
).
In conclusion, differentiating type spermatogonia have a strictly determined cell
cycle while A
s
, A
pr
, and A
al
spermatogonia have a rather variable cell cycle time indi-
cating that the proliferation of the latter cells is subject to regulation. The minimal cell
cycle time of A
s
, A
pr
, and A
al
spermatogonia is longer than that of differentiating type
spermatogonia. In rats and Chinese hamsters the duration of the minimal cell cycle of
the A
s,pr,al
spermatogonia is about one third longer than that of the differentiating type
spermatogonia. It is tempting to speculate that the cell cycle time of the A
s,pr,al
sper-
matogonia in mice will then be between 38 and 45 h, depending on the strain.
4.7
The Occurrence of “False” Pairs of Spermatogonia
As already indicated by Huckins, when A
s
spermatogonia carry out a division and
two new A
s
spermatogonia are formed in a self-renewing division, the daughter
cells will need time to migrate away from each other (Huckins
1971c, d
). As long
as these cells are within 25 mm from each other, they will be counted as A
pr
sper-
matogonia. These cells have been called a “false” pair (Fig.
4.2f
). As not much is
known about the speed at which the daughter stem cells migrate away from each
other, the number of false pairs cannot be determined.
In addition to false pairs occurring because of the time required to migrate away
from each other, the decision of daughter cells to stay together as a pair or to migrate
away from each other and become new stem cells may not have to take place directly
after division. In the
3
H-thymidine incorporation studies in the Chinese hamster, an
imbalance was found between the numbers of labeled metaphases of A
s
and of A
pr
spermatogonia. There were 100 metaphases of A
s
against 175 of A
pr
spermatogonia,
while in steady state kinetics these numbers should be similar (Lok et al.
1983
).
Also, more labeled interphase A
pr
than A
s
spermatogonia were found (Lok and de
Rooij
1983b
). It was speculated that at division some A
pr
spermatogonia lose their
bridge and split into new pairs or even into A
s
spermatogonia. In this respect, it is
interesting that GFRA1, one of the receptors for GDNF that stimulates SSC self-
renewal, is expressed by most A
s
and A
pr
spermatogonia, and gradually becomes less
expressed in A
al
spermatogonia when chain length increases (Tokuda et al.
2007
;
Hofmann et al.
2005
; Meng et al.
2000
). This suggests that some A
pr
spermatogonia
may be still be similar to A
s
spermatogonia at the molecular level.
Clearly, the nature of the A
pr
spermatogonia with respect to differentiation status
and self-renewing capacity needs to be studied in more detail. Unfortunately, progress
Search WWH ::
Custom Search