Biomedical Engineering Reference
In-Depth Information
2 years to reach pre-irradiation levels after a single dose of 1 Gy (Meistrich and van
Beek
1990
) and longer after higher doses of irradiation (Paulsen
1973
).
The recovery of sperm counts reflects the survival and regeneration of the stem
spermatogonia to some extent after low doses of irradiation (£1 Gy). The nadir of
sperm count occurs about 6 months after irradiation and there is progressive recov-
ery of sperm counts after that. But at this time, the ratio of spermatocytes to sper-
matogonia is tenfold lower than control levels (Meistrich and van Beek
1990
),
indicating that spermatogonial differentiation is not blocked but there is a reduced
efficiency of production of differentiated cells.
There seems to be a dissociation between the presence of stem spermatogonia
and recovery of sperm count after higher radiation doses. There are also occasional
examples where histological analysis of testes following treatment with chemo-
therapy reveals tubule cross-sections containing only spermatogonia (Kreuser et al.
1989
). In addition, testicular sperm are present in nearly half of the azoospermic
post-chemotherapy patients undergoing testicular sperm extraction for fertility treat-
ments (Chan et al.
2001
). Spontaneous recovery of sperm production can occur at
about 1 or 2 years after 2 Gy or 4-6 Gy of radiation given as single fractions
(Fig.
9.3
) (Clifton and Bremner
1983
; Rowley et al.
1974
). Individuals can also
completely recover sperm production after being azoospermic for 2-5 years after
toxicant exposure (Marmor et al.
1992
; Meistrich et al.
1992
; Potashnik and Porath
1995
; Pryzant et al.
1993
). It has been suggested that the numbers of stem sper-
matogonia must first reach a critical number for differentiation to take place; how-
ever, this cannot be the complete explanation (Meistrich and van Beek
1990
; Paulsen
1973
; Rowley et al.
1974
). The observation in rats that radiation damages the
somatic environment of the testis, which blocks the differentiation of spermatogonia
(Zhang et al.
2006
), may also apply to this situation in humans. The somatic damage
may cause the failure of differentiation of spermatozoa from spermatogonia but may
spontaneously resolve itself in the human testis after several years.
9.6
Modulation of the Regenerative Process
The use of hormone suppression treatments to reduce gonadotropins (FSH and LH)
and intratesticular testosterone levels were originally based on the hypothesis that
these treatments would protect the survival of stem spermatogonia from killing by
cytotoxic treatments and thereby enhance the subsequent recovery of spermatogen-
esis (Glode et al.
1981
). However, studies in rats disproved this theory; on the
contrary, hormone suppression does not alter spermatogonial kinetics (Meistrich
et al.
1997b
) or stem spermatogonial survival, but protects or enhances the subse-
quent ability of the somatic cells of the testis to support the recovery of spermato-
genesis from surviving stem spermatogonia (Meistrich et al.
2000
; Zhang et al.
2006
).
Although protection of spermatogenesis in mice from cyclophosphamide by treat-
ment with a GnRH (gonadotropin releasing hormone) agonist before and during
chemotherapy was claimed (Glode et al.
1981
), later studies failed to reproduce those
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