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This Article Full Text Full Text (PDF) All Versions of this Article: 69/6/1989    most recent biolreprod.103.020859v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Atchison, F. W. Articles by Means, A. R. Search for Related Content PubMed PubMed Citation Articles by Atchison, F. W. Articles by Means, A. R. Agricola Articles by Atchison, F. W. Articles by Means, A. R.

Spermatogonial Depletion in Adult Pin1-Deficient Mice¹

Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710

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 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 mo 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.

¹ This work was supported by National Institutes of Health grant CA-82845 (to A.R.M.) and by the Medical Scientist Training Program from the National Institutes of Health (to F.W.A.).

² Correspondence: Anthony R. Means, Department of Pharmacology and Cancer Biology, Box 3813, Duke University Medical Center, Durham, NC 27710. FAX: 919 681 7767; means001{at}mc.duke.edu

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