title: Overexpression of ubiquitin carboxyl-terminal hydrolase L1 arrests spermatogenesis in transgenic mice.
abstract: Ubiquitin carboxyl-terminal hydrolase 1 (UCH-L1) can be detected in mouse testicular germ cells, mainly spermatogonia and somatic Sertoli cells, but its physiological role is unknown. We show that transgenic (Tg) mice overexpressing EF1alpha promoter-driven UCH-L1 in the testis are sterile due to a block during spermatogenesis at an early stage (pachytene) of meiosis. Interestingly, almost all spermatogonia and Sertoli cells expressing excess UCH-L1, but little PCNA (proliferating cell nuclear antigen), showed no morphological signs of apoptosis or TUNEL-positive staining. Rather, germ cell apoptosis was mainly detected in primary spermatocytes having weak or negative UCH-L1 expression but strong PCNA expression. These data suggest that overexpression of UCH-L1 affects spermatogenesis during meiosis and, in particular, induces apoptosis in primary spermatocytes. In addition to results of caspases-3 upregulation and Bcl-2 downregulation, excess UCH-L1 influenced the distribution of PCNA, suggesting a specific role for UCH-L1 in the processes of mitotic proliferation and differentiation of spermatogonial stem cells during spermatogenesis.
authors.affiliation: Department of Degenerative Neurological Diseases, National Institute of Neuroscience, NCNP, Kodaira, Tokyo, Japan.
authors.forename: Yu-Lai
authors.initials: YL
authors.lastname: Wang
authors.forename: Wanzhao
authors.initials: W
authors.lastname: Liu
authors.forename: Ying-Jie
authors.initials: YJ
authors.lastname: Sun
authors.forename: Jungkee
authors.initials: J
authors.lastname: Kwon
authors.forename: Rieko
authors.initials: R
authors.lastname: Setsuie
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Osaka
authors.forename: Mami
authors.initials: M
authors.lastname: Noda
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Aoki
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yoshikawa
authors.forename: Keiji
authors.initials: K
authors.lastname: Wada
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D007150:Immunohistochemistry; D007248:Infertility, Male / Q000201:enzymology / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D025821:Polyubiquitin / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012708:Sertoli Cells / Q000378:metabolism; D013090:Spermatocytes / Q000166:cytology / Q000201:enzymology; D013091:Spermatogenesis / Q000502:physiology*; D025801:Ubiquitin / Q000378:metabolism; D043222:Ubiquitin Thiolesterase / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D015854:Up-Regulation / Q000235:genetics; D014746:Vimentin / Q000096:biosynthesis / Q000235:genetics
chemical_list: D018809:Proliferating Cell Nuclear Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; C482860:UCHL1 protein, human; D025801:Ubiquitin; D014746:Vimentin; D025821:Polyubiquitin; D043222:Ubiquitin Thiolesterase; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases