Biomedical Engineering Reference
In-Depth Information
66 Mya (million years ago)
41 Mya
23 Mya
Mouse
Rat
Human
Macaque
Fig. 9.1 Evolutionary distances between mice, rats, macaques, and humans
who have been cured of these diseases, the quality of life, which includes the ability
to have a normal child, then becomes a major issue. The major concern is the
prolonged reduction in sperm count to the point of azoospermia, as endocrine
dysfunction (e.g., testosterone reduction) only occurs in limited instances (Shalet
et al. 1989 ) and damage to other aspects of sperm function, such as loss of motility
or morphological abnormalities are less pronounced than the loss of sperm produc-
tion (Gandini et al. 2006 ; Meistrich et al. 1992 ). When sperm count recovers
following cytotoxic therapy, fertility is generally restored. However, when the dam-
age is severe, sperm count sometimes plateaus in an oligospermic range and the
sperm may have morphological abnormalities (Anserini et al. 2002 ), both of which
may be incompatible with fertility.
The adverse effects of chemotherapeutics and radiation on sperm production
have been studied in mice, rats, macaque monkeys, and human patients undergoing
treatment. Although many aspects of spermatogenesis and its regulation are con-
served across mammalian species, interspecies differences can result in variations
in response to and recovery from gonadotoxic therapies. Quantitative interspecies
comparisons are best done using radiation, because similar doses to the target organ
can be compared (Meistrich 1989, 1992 ). In this chapter, when the species is not
designated, this will represent general principles across these four species; we will
clarify which aspects apply to a more limited subset of them. Although it is
expected that the primates will be more similar to each other and the same for
rodents, the evolutionary distance between humans and macaques is 35% of that
between rodents and primates (Fig. 9.1 ) (Kumar and Hedges 1998 ). Thus, some
limited aspects in the response of the human testis to a gonadotoxic insult might
possibly be more similar to one of the rodents than to macaques. Overall, there
must be unifying biological processes that dictate the regenerative capacity of sper-
matogonial stem cells after injury, but there are likely to be details that differ
between species (Meistrich 1992 ) causing the different outcomes.
9.2
Immediate and Short-Term Effects of Gonadotoxic
Therapies
The sequence of spermatogenic cells consists of the stem spermatogonia, differen-
tiating spermatogonia, spermatocytes, spermatids, and spermatozoa. Among these
cells, the differentiating spermatogonia proliferate most actively and are extremely
 
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