Biomedical Engineering Reference
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the A s and A pr of rodents (Hermann et al. 2009 ). However, there are important
kinetic differences. The A dark spermatogonia are largely nonproliferative (Clermont
and Antar 1973 ; Ehmcke et al. 2005b ), whereas in rodents all of the A s spermatogo-
nia are proliferative (Huckins 1971b ). Furthermore, whereas in rodents the majority
of the stem cells are single A spermatogonia, in primates the self-renewing A pale
spermatogonia usually have a minimum clonal size of two or four cells (Ehmcke
et al. 2005a ).
Although killing of stem spermatogonia may also be determined indirectly by
the prolonged reduction of recovery of sperm production, this assay can be differ-
entially affected by the efficiency of recovery of spermatogenesis from surviving
stem cells in different species. Whereas in mice, there is an excellent correlation
between stem cell survival and sperm counts, in some cases in rats, there may be a
complete block in the differentiation of surviving stem cells, resulting in no sperm
being produced despite surviving stem cells. In the limited studies done with mon-
keys, sperm count recovery appears to reflect the stem cell killing. Although in
human, prolonged azoospermia is observed despite the presence of surviving stem
cells, the duration of azoospermia may be an indicator of the degree of stem cell
killing. Nevertheless these assays do appear to show interspecies differences in the
sensitivity of stem spermatogonia to some chemotherapeutic drugs. In particular,
rodent stem cells are more resistant than those in human to killing by cyclophosph-
amide and cisplatin, but are more sensitive to killing by doxorubicin. The reasons
for these differences are not known.
There appear to be some interspecies differences in regeneration of stem cell
number. In mice, there are data indicating immediate progressive recovery of stem
cell number after radiation and busulfan and other data indicating that, in the case
of radiation, there may then be some decline until 2 months later, followed by pro-
gressive recovery. In irradiated monkeys and humans there are clear declines in the
numbers of type A spermatogonia lasting about 3 and 6 months, respectively, after
which recovery begins.
The recovery of spermatogenesis from surviving stem cells shows major inter-
and intra-species differences. The initiation of differentiation appears to occur quite
rapidly (within 1 week) from surviving stem cells in the mouse. In rats, rapid initia-
tion of differentiation occurs in some cases, but in other situations depending on the
strain, dose, and toxicant there is a prolonged (at least 60-week) block in the ability
of the somatic environment to support spermatogonial differentiation. In monkeys
there is an initial period of about 2-3 months during which type A spermatogonia
show little differentiation, but subsequently spermatogonia differentiate without a
block. In human, the prolonged absence of sperm in the ejaculate followed by
excellent recovery of sperm counts indicates that there is a block at some point in
the differentiation or sperm transport process.
The dramatic stimulation of recovery of spermatogenesis by hormone suppres-
sion in toxicant-treated rats is in contrast to the less marked effects observed in
mice, the absence of stimulation in macaques, and generally negative but variable
results in human. One contribution to this difference may be the interspecies differ-
ences in the block in differentiation of spermatogonia. This block is most dramatically
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