Biomedical Engineering Reference
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allows estimation of androgen production by the grafted tissue. Androgenic activity
of the grafted testicular tissue can be monitored by serum androgen levels or the
size of the host seminal vesicles that are highly sensitive to androgens (Gosden and
Aubard
1996a
). In addition, removal of the host gonads releases the negative feed-
back of the recipient's gonad on the pituitary resulting in increased levels of FSH
after grafting (Schlatt et al.
2003
). Increased gonadotropin stimulation may support
Sertoli cell proliferation and graft development until a feedback axis is reestab-
lished between the grafted tissue and the host hypothalamus and pituitary.
Xenografting of hamster tissue into young and old nude mice was performed to
explore a potential impact of the recipient's age. This study revealed a surprisingly
better outcome of graft survival and function in older mice (Ehmcke et al.
2008
).
Less efficient immunological interference or a change in the endocrine milieu in
aged recipients might be reasons for this unexpected finding.
Other factors that affect testis tissue survival and function after transplantation are
the donor species, and the developmental or functional stage of the donor testis. The
time to achieve full maturation of immature testicular tissue and the number of tubules
displaying full spermatogenesis after grafting depends on the donor species. While in
grafts from rodent tissue (mouse, hamster, rat) it takes only several weeks until sperm
are generated, the period until active spermatogenesis occurs and first elongated sper-
matids can be observed is several months in grafts of larger species. However, time to
the first appearance of spermatids is generally advanced when compared with normal
tissue in situ. Such an acceleration of testicular development is especially notable in
species with long periods until onset of puberty and is attributed to the immediate
response of the xenografts to the host gonadotropins. Two examples of this are xeno-
grafts of immature pigs and monkeys (Honaramooz et al.
2002, 2004
), while two
notable exceptions are grafts from cattle and cats. In cattle, onset of spermatogenesis
is slightly advanced or similar to testes in situ (Oatley et al.
2004, 2005
; Rathi et al.
2005
). In cats, onset of spermatogenesis in xenografts is delayed (Snedaker et al.
2004
;
Kim et al.
2007
). It therefore appears that xenografting can accelerate testicular matu-
ration by premature initiation of pubertal development in 1- to 2-year-old macaques
but not by acceleration of pubertal maturation (Table
10.2
). Interestingly, even bovine
and feline xenografts that show a delay in full development initiate pubertal differentia-
tion prematurely until the onset of meiosis when compared to age-matched in situ
controls. However, bovine germ cells in xenografts frequently arrest at meiosis with
only a small percentage of tubules producing elongated spermatids (Rathi et al.
2005
).
In cats, delay of testicular maturation appears to be controlled by intrinsic factors of
the grafted tissue and may indicate a delayed development of specific components
(Snedaker et al.
2004
; Kim et al.
2007
).
The efficiency of spermatogenesis in xenografts is also species dependent. While
the number of spermatozoa produced by pig and goat testicular xenografts was simi-
lar to that produced in normal testes on a “per gram of tissue” basis (Honaramooz
et al.
2002
), complete spermatogenesis does not occur in all seminiferous tubules in
xenografts of cattle (Oatley et al.
2004, 2005
; Rathi et al.
2005
; Schmidt et al.
2006a, b
), horses (Rathi et al.
2006
), cats (Snedaker et al.
2004
; Kim et al.
2007
)
sheep (Zeng et al.
2006
; Arregui et al.
2008a
; Rodriguez-Sosa et al.
2010
), and
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