Overexpression of ubiquitin carboxyl-terminal hydrolase L1 arrests spermatogenesis in transgenic mice
Overexpression of ubiquitin carboxyl-terminal hydrolase L1 arrests spermatogenesis in transgenic mice
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DOI：
10.1002/mrd.20364
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发表时间：
2006-01-01
影响因子：
2.5
通讯作者：
Wada, K
中科院分区：
文献类型：
--
作者：
Wang, YL;Liu, WZ;Wada, K
泛素羧基末端水解酶1（UCH-L1）可在小鼠睾丸生殖细胞（主要是精原细胞和支持细胞）中检测到，但其生理作用尚不清楚。我们发现，转基因（Tg）小鼠在睾丸中过表达EF 1 α启动子驱动的LICH-L1是不育的，由于在减数分裂的早期阶段（粗线期）的精子发生过程中的块。有趣的是，几乎所有的精原细胞和支持细胞表达过量UCH-L1，但很少PCNA（增殖细胞核抗原），没有表现出凋亡或TUNEL阳性染色的形态学迹象。相反，生殖细胞凋亡主要是在初级精母细胞中检测到有弱或负UCH-L1表达，但强PCNA表达。这些数据表明，UCH-L1的过度表达影响减数分裂过程中的精子发生，特别是诱导初级精母细胞凋亡。除了caspase-3上调和Bcl-2下调的结果外，过量的UCH-L1影响PCNA的分布，表明UCH-L1在精子发生过程中精原干细胞的有丝分裂增殖和分化过程中的特定作用。
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 over-expressing EF1 alpha promoter-driven LICH-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.