Accelerated impairment of spermatogenic cells in sod1-knockout mice under heat stress
Accelerated impairment of spermatogenic cells in sod1-knockout mice under heat stress
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DOI：
10.1080/10715760500130517
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发表时间：
2005-07-01
影响因子：
3.3
通讯作者：
Fujii, J
中科院分区：
文献类型：
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作者：
Ishii, T;Matsuki, S;Fujii, J
对于正常的精子发生，阴囊的温度低于身体的温度。哺乳动物睾丸由于暴露于热而经历细胞死亡的机制仍然是一个有争议的问题。由于热应激过程中产生活性氧（ROS），并参与生精细胞损伤的假设，我们诱导实验性隐睾症的SOD1基因敲除小鼠的睾丸，并检查基因缺陷的影响。通过TUNEL染色判断，SOD1敲除小鼠睾丸细胞中DNA的裂解比野生型小鼠早。为了证实SOD 1对热应激的这种高敏感性的反应性，从SOD 1敲除小鼠和野生型小鼠中分离生精细胞，并在32.5和378 ℃下培养。从SOD1敲除小鼠中分离的细胞在两种温度下都比野生型小鼠更脆弱。培养的大鼠生精细胞暴露于ROS诱导线粒体释放细胞色素c，而支持细胞在相同条件下更有抵抗力。Tiron是一种超氧化物清除剂，它能抑制热诱导的线粒体细胞色素c的释放。总的来说，这些数据表明，ROS在热应激过程中产生，并导致生精细胞死亡。或者，由于即使是短时间的暴露也会引发对生精细胞的有害损伤，因此产生的ROS可能作为细胞死亡的一种信号而不是直接导致对细胞的氧化损伤。
For normal spermatogenesis, the temperature of the scrotum is lower than that of the body. The mechanism by which mammalian testes undergoes cell death as the result of exposure to heat continues to be a matter of debate. Since generation of reactive oxygen species (ROS) during heat stress and involvement in spermatogenic cell damage are postulated, we induced experimental cryptorchidism in the testes of SOD1-knockout mice and examined effects of the gene deficiency. The cleavage of DNA in testicular cells, as judged by TUNEL staining, were elevated in SOD1-knockout mice at an earlier stage than in the wild-type mice. To confirm responsiveness of SOD1 for this high susceptibility to heat stress, spermatogenic cells were isolated from SOD1-knockout and wildtype mice and cultured at 32.5 and 378 degrees C. The cells isolated from SOD1-knockout were more vulnerable at both temperatures than those from wild-type mice. The exposure of cultured rat spermatogenic cells to ROS induced the release of cytochrome c from mitochondria, while Sertoli cells were more resistant under the same conditions. Tiron, a superoxide scavenger, suppressed the heat induced release of cytochrome c from mitochondria. Collectively, these data suggest that ROS are generated during heat stress and cause spermatogenic cell death. Alternatively, since even a short exposure triggers harmful damage to spermatogenic cells, generated ROS may function as a type of signal for cell death rather than directly causing oxidative damage to cells.