Guo Maowu, Sato Eimei, Li Xiang, Mori Etsuko, Saito Shigeru, Mori Tsuneatsu
Department of Immunology, Institute of Medical Science, University of Tokyo, Japan.
Zygote. 2002 Feb;10(1):17-22. doi: 10.1017/s0967199402002034.
The molecular mechanisms leading to ovarian follicular atresia in the typical pathways of programmed cell death remain to be clarified. Here we have demonstrated that the apoptotic signalling pathway in MRL-+/+ (MRL/+) murine oocytes is through the Fas receptor followed by the activation of caspase-3. In contrast, we found that the aberrant expression and dysfunction of the mutant Fas receptor in MRL-lpr/lpr (MRL/lpr) murine oocytes caused by insertion of the early transposable element (ETn) into the Fas gene were associated with an inability to activate the caspase cascade (especially caspase-3) and to induce nuclear DNA fragmentation. These findings indicate that the induction of apoptosis in MRL/lpr murine oocytes did not occur in the presence of a defective Fas receptor lacking the death domain to trigger the caspase cascade, suggesting a failure to induce ovarian follicular atresia.
导致卵巢卵泡闭锁的典型程序性细胞死亡途径中的分子机制仍有待阐明。在此，我们已经证明，MRL-+/+（MRL/+）小鼠卵母细胞中的凋亡信号通路是通过Fas受体，随后激活caspase-3。相比之下，我们发现，由于早期转座元件（ETn）插入Fas基因而导致的MRL-lpr/lpr（MRL/lpr）小鼠卵母细胞中突变Fas受体的异常表达和功能障碍，与无法激活caspase级联反应（尤其是caspase-3）以及诱导核DNA片段化有关。这些发现表明，在缺乏死亡结构域以触发caspase级联反应的缺陷Fas受体存在的情况下，MRL/lpr小鼠卵母细胞中不会发生凋亡诱导，这表明无法诱导卵巢卵泡闭锁。
