Overexpression of ubiquitin carboxyl-terminal hydrolase L1 arrests spermatogenesis in transgenic mice.
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.
Wang
Yu-Lai
YL
Department of Degenerative Neurological Diseases, National Institute of Neuroscience, NCNP, Kodaira, Tokyo, Japan.
Liu
Wanzhao
W
Sun
Ying-Jie
YJ
Kwon
Jungkee
J
Setsuie
Rieko
R
Osaka
Hitoshi
H
Noda
Mami
M
Aoki
Shunsuke
S
Yoshikawa
Yasuhiro
Y
Wada
Keiji
K
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
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