Biomedical Engineering Reference
In-Depth Information
Keywords
Spermatogenesis • Xenografting • Stem cells • Fertility preservation
10.1
Introduction
Spermatogonial stem cells sustain the male germ lineage. They represent a pool of
diploid reserve germ cells for reconstitution of spermatogenesis [for review see Ehmcke
et al. (
2006
)] and contain the genetic material that is transmitted to the next generation.
In most systems studied so far, stem cells reside in a specialized environment, called
the stem cell niche, which governs their proliferation and differentiation. The existence
of a testicular stem cell niche is well documented but its cellular and molecular com-
ponents are poorly understood and might vary between species. However, settlement
and colonization of testicular stem cells from a large variety of species in the mouse
testis reveals that stem cell recognition and colonization are highly conserved among
different species (Dobrinski et al.
2000
). The importance of the niche and its plasticity
to accept various germline cells has been demonstrated. In addition to spermatogonia,
primordial germ cells or teratocarcinoma cells have the potential to enter the niche and
initiate spermatogenesis (Nayernia et al.
2004
; Chuma et al.
2005
).
In primate testes, three types of spermatogonia are distinguished by morphological
criteria: A
dark
, A
pale
, and B spermatogonia (Clermont and Leblond
1959
; Clermont
1966, 1969
). The number of subsequent divisions of B-spermatogonia differ
between primate species. For example, one division is described in men and four
divisions (B1-B4) in macaques. Various models for spermatogonial kinetics have
been described and are currently under debate, signifying that the exact details of
spermatogonial turnover in the primate testis are still largely unresolved (Ehmcke
and Schlatt
2006
; Amann
2008
). However, it is generally agreed that A
dark
spermatogonia are mitotically quiescent and act as reserve stem cells since they
become proliferatively active during pubertal expansion (Simorangkir et al
.
2005
)
and following depletion of spermatogonia due to irradiation or toxic exposure (van
Alphen et al.
1988, 1989
). On the other hand, A
pale
spermatogonia proliferate regu-
larly and are considered self renewing progenitors (Ehmcke et al.
2005a, b
).
Rapidly dividing premeiotic germ cells are highly sensitive to irradiation and
toxins in adult and immature monkeys (van Alphen et al.
1989
; Jahnukainen et al
.
2006a
). Low doses of cytotoxic drugs or irradiation deplete the differentiating sper-
matogonia while less sensitive spermatogonial stem cells as well as spermatocytes
and spermatids survive. Recovery of spermatogenesis occurs from the remaining
stem cells and relies on the type, dose, and fractionation of cytotoxic drugs and
irradiation (van Alphen et al.
1988
). During recovery, testicular histology reveals an
all-or-nothing pattern with areas of full spermatogenesis and areas with a Sertoli-
cell-only pattern. This histological pattern during spermatogenic recovery indicates
a critical role of spermatogonial stem cells for re-initiation of spermatogenesis and
shows that under doses used in these studies in primates the somatic environment is
not heavily affected by chemotherapy or radiation exposure (Schlatt et al.
2009
).
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