title: Ubiquitin C-terminal hydrolase L-1 is essential for the early apoptotic wave of germinal cells and for sperm quality control during spermatogenesis.
abstract: 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.
authors.affiliation: Department of Degenerative Neurological Disease, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.
authors.forename: Jungkee
authors.initials: J
authors.lastname: Kwon
authors.forename: Keiji
authors.initials: K
authors.lastname: Mochida
authors.forename: Yu-Lai
authors.initials: YL
authors.lastname: Wang
authors.forename: Satoshi
authors.initials: S
authors.lastname: Sekiguchi
authors.forename: Tadashi
authors.initials: T
authors.lastname: Sankai
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Aoki
authors.forename: Atsuo
authors.initials: A
authors.lastname: Ogura
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yoshikawa
authors.forename: Keiji
authors.initials: K
authors.lastname: Wada
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D005854:Germ Cells / Q000201:enzymology; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013081:Sperm Motility / Q000502:physiology; D013091:Spermatogenesis / Q000502:physiology*; D013094:Spermatozoa / Q000201:enzymology* / Q000502:physiology; D013737:Testis / Q000201:enzymology* / Q000502:physiology; D043222:Ubiquitin Thiolesterase / Q000235:genetics / Q000502:physiology*; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
chemical_list: C494827:Bax protein, mouse; C494812:Bcl2l1 protein, mouse; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D043222:Ubiquitin Thiolesterase; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases