HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 74/6/1026    most recent biolreprod.105.044610v1 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 Zheng, S. Articles by Lysiak, J. J. Search for Related Content PubMed PubMed Citation Articles by Zheng, S. Articles by Lysiak, J. J. Agricola Articles by Zheng, S. Articles by Lysiak, J. J.

Caspase 2 Activity Contributes to the Initial Wave of Germ Cell Apoptosis During the First Round of Spermatogenesis¹

Departments of Urology³ and Cell Biology,⁴ University of Virginia Health Science System, Charlottesville, Virginia 22908

ABSTRACT

Early in postnatal life the first phase of spermatogenesis is accompanied by an initial wave of germ cell apoptosis. This wave of germ cell death is thought to reflect an adjustment of germ cell numbers that can be adequately maintained by Sertoli cells. Caspase 2 is an initiator caspase whose activation has been found to stimulate apoptosis through the mitochondria. The present study investigates if germ cell apoptosis during the first phase of spermatogenesis involves activation of caspase 2. Germ cell apoptosis was found to peak at Postnatal Days (pnds) 15 and 16 in male C57BL/6 mice. Western blot analysis revealed that caspase 2 also increased in the testes at pnd 16. Immunolocalization of total caspase 2 showed staining of germ cells in the periphery of the seminiferous tubules as well as germ cells more centrally located in an area where apoptotic germ cells were observed. Cytoplasmic as well as nuclear staining was observed. Western blot analysis of cytoplasmic and nuclear proteins from pnd 16 testis revealed pro-caspase 2 in both fractions. Further Western blot analysis for caspase 2 detected an increase in the activation of caspase 2 at pnd 16 in proteins isolated from the cytoplasm but not from the nucleus. Proteins isolated from mitochondria from pnd 16 testes revealed an increase in pro-caspase 2 as well as activated caspase 2 corresponding with an increase in cytochrome c in cytoplasmic fractions. Injection of the caspase 2-specific inhibitor z-VDVAD-fmk directly into the testis significantly reduced the observed germ cell apoptosis at pnds 15 and 16. These results suggest that caspase 2 is present in germ cells in the murine testis in early postnatal life and increases in expression in correspondence to the initial wave of germ cell apoptosis. Caspase 2 also localizes to mitochondria, where it is correlated with a release of cytochrome c and germ cell apoptosis. Blockade of caspase 2 activation reduced the number of apoptotic germ cells in the initial wave of germ cell apoptosis, indicating that caspase 2 plays an important role upstream of the mitochondria in germ cell apoptosis during the first phase of spermatogenesis.

apoptosis, gamete biology, spermatogenesis, testis

¹ Supported by P50 DK45179 (J.J.L.), R01 DK53072 (T.T.T.), and a UVA Research and Development Grant (J.J.L.).

² Correspondence: FAX: 434 924 8311; jl6n{at}virginia.edu

This article has been cited by other articles:

				J.-B. Stukenborg, J. Wistuba, C. M. Luetjens, M. A. Elhija, M. Huleihel, E. Lunenfeld, J. Gromoll, E. Nieschlag, and S. Schlatt Coculture of Spermatogonia With Somatic Cells in a Novel Three-Dimensional Soft-Agar-Culture-System J Androl, May 1, 2008; 29(3): 312 - 329. [Abstract] [Full Text] [PDF]

				R. Lagos-Cabre and R. D Moreno Mitotic, but not meiotic, oriented cell divisions in rat spermatogenesis Reproduction, April 1, 2008; 135(4): 471 - 478. [Abstract] [Full Text] [PDF]