Submitted June 30, 2003
Returned for revision July 15, 2003
Accepted August 6, 2003
Testis
Spermatogonial Depletion in Adult Pin1-Deficient
Mice
Fawn W. Atchison *
and
Anthony R. Means
* To whom correspondence should be addressed. E-mail: fwa{at}duke.edu.
Abstract
Spermatogonia in the mouse testis arise from early
postnatal gonocytes that are derived from primordial germ
cells (PGCs) during embryonic development. The
proliferation, self-renewal, and differentiation of
spermatogonial stem cells provide the basis for the
continuing integrity of spermatogenesis. We previously
reported that Pin1-deficient embryos had a
profoundly reduced number of PGCs, and that Pin1
was critical to ensure appropriate proliferation of
PGCs. The current investigation aimed to elucidate the
function of Pin1 in postnatal germ cell
development by analyzing spermatogenesis in adult
Pin1-/- mice. Although Pin1 was
ubiquitously expressed in the adult testis, we found it
to be most highly expressed in spermatogonia and in
Sertoli cells. Correspondingly, we show here that
Pin1 plays an essential role in maintaining
spermatogonia in the adult testis. Germ cells in
postnatal Pin1-/- testis were able
to initiate and complete spermatogenesis, culminated by
production of mature spermatozoa. However, there was a
progressive and age-dependent degeneration of the
spermatogenic cells in Pin1-/- testis
that led to complete germ cell loss by 14 months of age.
This depletion of germ cells was not due to increased
cell apoptosis. Rather, detailed analysis of the
seminiferous tubules using a germ cell specific marker
revealed that depletion of spermatogonia was the first
step in the degenerative process, and led to disruption
of spermatogenesis, which resulted in eventual tubule
degeneration. These results reveal that the presence of
Pin1 is required to regulate proliferation and/or
cell fate of undifferentiated spermatogonia in the adult
mouse testis.
Key words:
Testis •
Sertoli cells •
Spermatogenesis
