Ubiquitin C-terminal hydrolase L-1 is essential for the early apoptotic wave of germinal cells and for sperm quality control during spermatogenesis
Ubiquitin C-terminal hydrolase L-1 is essential for the early apoptotic wave of germinal cells and for sperm quality control during spermatogenesis
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DOI：
10.1095/biolreprod.104.037077
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发表时间：
2005-07-01
影响因子：
3.6
通讯作者：
Wada, K
中科院分区：
文献类型：
--
作者：
Kwon, J;Mochida, K;Wada, K
泛素化在哺乳动物精子发生的各个发育阶段都是必需的。泛素C-末端水解酶（UCH）L1被认为与单泛素结合以控制泛素水平。以前，我们发现UCHL 1缺陷的gad小鼠睾丸泛素水平降低，并对隐睾应激相关损伤有抵抗力。在这里，我们分析了UCHL 1在第一轮精子发生和精子成熟过程中的功能，这两个过程都需要泛素介导的蛋白水解。gad小鼠未成熟睾丸中的睾丸生殖细胞对第一轮精子发生过程中出现的早期凋亡波具有抵抗力。TUNEL染色和细胞定量显示，出生后第7天至第14天，gad小鼠的生殖细胞凋亡减少，减数分裂前生殖细胞数量增加。凋亡蛋白TRP 53、Bax和caspase-3的表达在gad小鼠的未成熟睾丸中也显著降低。在成年gad小鼠中，附睾尾重量、附睾中精子数量和精子活力降低。此外，有缺陷的精子数量显着增加，但没有检测到完全不育。这些数据表明，UCHL 1是正常的精子发生和精子质量控制所必需的，并证明了UCHL 1依赖的细胞凋亡在精原细胞和精子成熟中的重要性。
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.