Caspase 9 is constitutively activated in mouse oocytes and plays a key role in oocyte elimination during meiotic prophase progression.
Caspase 9 is constitutively activated in mouse oocytes and plays a key role in oocyte elimination during meiotic prophase progression.
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DOI：
10.1016/j.ydbio.2013.01.027
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发表时间：
2013-05-01
影响因子：
2.7
通讯作者：
Taketo, Teruko
中科院分区：
文献类型：
--
作者：
Ene, Adriana C.;Park, Stephanie;Edelmann, Winfried;Taketo, Teruko
在许多哺乳动物物种中，超过一半的初始卵母细胞群体被新生儿淘汰，从而限制了用于繁殖的卵母细胞储备。这种主要的卵母细胞损失的原因或机制仍然知之甚少。我们研究了野生型小鼠卵巢以及Msh 5 −/−卵巢中卵母细胞消除中涉及的凋亡途径，其中所有卵母细胞由于缺乏双链断裂修复而被消除。免疫印迹和免疫荧光染色显示，启动caspase 9和效应caspase 7组成型激活，在几乎所有的卵母细胞在胎儿卵巢，无论其基因型。在caspase 9 −/−卵巢中，卵母细胞的总数保持较高，而野生型卵巢在卵巢发育过程中稳步下降。因此，半胱天冬酶9的激活是卵母细胞死亡所必需的，但不会立即导致卵母细胞死亡。我们发现，XIAP，一种内源性的细胞凋亡抑制剂，也丰富的卵母细胞减数分裂前期进展。另一方面，PARP 1的切割形式，效应半胱天冬酶的靶点，定位于有限数量的卵母细胞的细胞核，并且在Msh 5 −/−卵巢中所有卵母细胞消失之前，切割的PARP 1阳性卵母细胞核的频率显著增加。我们的结论是，线粒体凋亡途径介导的半胱天冬酶9组成型激活的卵母细胞，并使消除卵母细胞减数分裂错误，这可以被捕获的PARP 1的裂解。
In many mammalian species, more than half of the initial oocyte population is eliminated by neonatal life, thus limiting the oocyte reserve for reproduction. The cause or mechanism of this major oocyte loss remains poorly understood. We examined the apoptotic pathway involved in oocyte elimination in wild-type mouse ovaries as well as in Msh5 −/− ovaries, in which all oocytes were eliminated due to a lack of double strand break repair. Immunoblot and immunofluorescence staining showed that an initiator caspase 9 and an effector caspase 7 were constitutively activated in almost all oocytes in fetal ovaries regardless of their genotypes. In caspase 9 −/− ovaries, the total number of oocytes remained high while that in wild-type ovaries steadily declined during ovarian development. Therefore, the activation of caspase 9 was required for but did not immediately lead to oocyte demise. We found that XIAP, an endogenous inhibitor of apoptosis, was also abundant in oocytes during meiotic prophase progression. On the other hand, a cleaved form of PARP1, a target of effector caspases, was localized to the nuclei of a limited number of oocytes, and the frequency of cleaved PARP1-positive oocyte nuclei increased significantly higher before all oocytes disappeared in Msh5 −/− ovaries. We conclude that the mitochondrial apoptotic pathway mediated by caspase 9 is constitutively activated in oocytes and renders the elimination of oocytes with meiotic errors, which can be captured by the cleavage of PARP1.
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影响因子：
3.6
作者：
Flaws, JA;Hirshfield, AN;Furth, PA
通讯作者：
Furth, PA
影响因子：
4
作者：
Alton, Michelle;Taketo, Teruko
通讯作者：
Taketo, Teruko
影响因子：
4
作者：
De Felici, M;Klinger, FG;Lobascio, M
通讯作者：
Lobascio, M
影响因子：
4.8
作者：
Matikainen, T;Perez, GI;Tilly, JL
通讯作者：
Tilly, JL
影响因子：
13.3
作者：
De Felici, Massimo;Lobascio, Anna Maria;Klinger, Francesca Gioia
通讯作者：
Klinger, Francesca Gioia