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Enhancement of germ cell apoptosis induced by ethanol in transgenic mice overexpressing Fas Ligand

机译:乙醇诱导过表达Fas配体的转基因小鼠生殖细胞凋亡的增强

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摘要

It was suggested that chronic ethanol exposure could result in testicular germ cell apoptosis, but the mechanism is still unclear. In the present study, we use a model of transgenic mice ubiquitously overexpressing human FasL to investigate whetherFas ligand plays a role in ethanol-induced testicular germ cell apoptosis. Both wild-type (WT) mice and transgenic (TG) mice were treated with acute ethanol (20 percent v/v) by introperitoneal injection for five times. After ethanol injection, WT mice displayed up-regulation of Fas ligand in the testes, which was shown by FTTC-conjugated flow cytometry and western blotting. Moreover, TG mice exhibited significantly more apoptotic germ cells than WT mice did after ethanol injection, which was demonstrated by DNA fragmentation, PI staining flow cytometry and TUNEL staining. In addition, histopathological examination revealed that degenerative changes of epithelial component of the tubules occurred in FasL overexpressing transgenic mice while testicular morphology was normal in wild-type mice after acute ethanol exposure, suggesting FasL expression determines the sensitivity of testes to ethanol in mice. In summary, we provide the direct evidences that Fas ligand mediates the apoptosis of testicular germcells induced by acute ethanol using FasL transgenic mice.
机译:有人提出慢性乙醇暴露可能导致睾丸生殖细胞凋亡,但其机制尚不清楚。在本研究中,我们使用普遍过量表达人FasL的转基因小鼠模型来研究Fas配体在乙醇诱导的睾丸生殖细胞凋亡中是否起作用。野生型(WT)小鼠和转基因(TG)小鼠均通过腹膜内注射用急性乙醇(20%v / v)处理五次。乙醇注射后,野生型小鼠在睾丸中显示出Fas配体的上调,这通过FTTC共轭流式细胞仪和Western blotting得以显示。而且,TG小鼠注射乙醇后,WT小鼠的凋亡生殖细胞明显多于WT小鼠,这可以通过DNA片段化,PI染色流式细胞仪和TUNEL染色来证明。此外,组织病理学检查显示,过量暴露于FasL的转基因小鼠中,小管的上皮成分发生了变性​​,而急性乙醇暴露后,野生型小鼠的睾丸形态正常,这表明FasL的表达决定了小鼠睾丸对乙醇的敏感性。总之,我们提供直接证据,证明FasL配体介导FasL转基因小鼠急性乙醇诱导的睾丸生殖细胞凋亡。

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