Biomedical Engineering Reference
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observed in rats. There is some evidence that there is a block in spermatogenic cell
differentiation in human males treated with gonadotoxic agents (Clifton and
Bremner
1983
; Kreuser et al.
1989
; Pryzant et al.
1993
). Although this can some-
times be reversed spontaneously, gradually over time, or perhaps by some unknown
perturbation, there is no consistent evidence that it can be reversed by hormone
suppression.
A second contribution to the interspecies difference in stimulation by hormone
suppression may be a result of differences in the effects of intratesticular testoster-
one and FSH on the normal progression of spermatogenesis. In normal rodents,
suppression of these hormones has very little effect on the development of sper-
matogonia to the spermatocyte stage. The first step in the stimulation of spermato-
genesis by hormone suppression in toxicant-treated rats is progression of
spermatogonial differentiation and spermatocyte formation; this may be necessary
to effectively “jump-start” the process. In contrast, in both normal monkeys and
humans, suppression of testosterone and FSH markedly inhibits the differentiation
of type A to type B spermatogonia (McLachlan et al.
2002
), but this effect appears
to be primarily a result of the FSH suppression (Simorangkir et al.
2009
). This
inability of spermatogonial differentiation to occur in hormone-suppressed pri-
mates may therefore explain the failure of hormone suppression to stimulate sper-
matogenic recovery in those species.
9.8
Conclusion
The observations of interspecies differences in sensitivity and recovery of sper-
matogenesis can lead to focusing future research to answer specific questions that
can improve our understanding of, and ability to enhance, spermatogenic recovery
in humans.
The failure of recovery in primates is in part due to the greater sensitivity of
human (and monkey) stem spermatogonia, compared to rodent stem spermatogo-
nia, to radiation and certain chemotherapeutic agents. Future research should focus
on elucidating the reasons for greater sensitivity of primate stem spermatogonia to
radiation and certain chemotherapeutic agents in order to develop methods to pro-
tect them.
The failure of recovery in primates also appears to be due to the slow repopula-
tion of the stem cell compartments and their inability to differentiate to produce
spermatozoa. This may be in part due to somatic damage to the stem cell niche and
the support of spermatogenic cell differentiation. Such damage to the somatic
support of differentiation is also most apparent in certain strains of rat. The results
of future research on the mechanisms involved in the spermatogonial block in rats
may therefore be applicable to stimulating recovery of spermatogenesis in humans
exposed to gonadotoxic agents.
Finally, the mechanism by which hormone suppression protects or reverses the
damage to the somatic elements of the testis to stimulate spermatogenic recovery
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