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This Article Full Text Full Text (PDF) All Versions of this Article: 73/1/29    most recent biolreprod.104.037077v1 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 My Folders Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kwon, J. Articles by Wada, K. Search for Related Content PubMed PubMed Citation Articles by Kwon, J. Articles by Wada, K. Agricola Articles by Kwon, J. Articles by Wada, K.

Ubiquitin C-Terminal Hydrolase L-1 Is Essential for the Early Apoptotic Wave of Germinal Cells and for Sperm Quality Control During Spermatogenesis¹

Department of Degenerative Neurological Disease,³ National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8502, Japan Department of Biomedical Science,⁴ Graduate School of Agricultural and Life Sciences, University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan Bioresource Engineering Division,⁵ Bioresource Center, Riken, Tsukuba, Ibaraki 305-0074, Japan Tsukuba Primate Center,⁶ National Institute of Infectious Diseases, Tsukuba, Ibaraki 305-0843, Japan

Ubiquitination is required throughout all developmental stages of mammalian spermatogenesis. Ubiquitin C-terminal hydrolase (UCH) L1 is thought to associate with monoubiquitin to control ubiquitin levels. Previously, we found that UCHL1-deficient testes of gad mice have reduced ubiquitin levels and are resistant to cryptorchid stress-related injury. Here, we analyzed the function of UCHL1 during the first round of spermatogenesis and during sperm maturation, both of which are known to require ubiquitin-mediated proteolysis. Testicular germ cells in the immature testes of gad mice were resistant to the early apoptotic wave that occurs during the first round of spermatogenesis. TUNEL staining and cell quantitation demonstrated decreased germ cell apoptosis and increased numbers of premeiotic germ cells in gad mice between Postnatal Days 7 and 14. Expression of the apoptotic proteins TRP53, Bax, and caspase-3 was also significantly lower in the immature testes of gad mice. In adult gad mice, cauda epididymidis weight, sperm number in the epididymis, and sperm motility were reduced. Moreover, the number of defective spermatozoa was significantly increased; however, complete infertility was not detected. These data indicate that UCHL1 is required for normal spermatogenesis and sperm quality control and demonstrate the importance of UCHL1-dependent apoptosis in spermatogonial cell and sperm maturation.

apoptosis, early apoptotic wave, epididymis, gad mouse, sperm, spermatogenesis, sperm quality, testis, UCHL1

² Correspondence: Keiji Wada, Department of Degenerative Neurological Disease, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8502, Japan. FAX: 81 42 341 1745; wada{at}ncnp.go.jp

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