Overexpression of cyclin A1 promotes meiotic resumption but induces premature chromosome separation in mouse oocyte

Overexpression of cyclin A1 promotes meiotic resumption but induces premature chromosome separation in mouse oocyte
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细胞周期蛋白 A1 的过度表达促进减数分裂恢复,但诱导小鼠卵母细胞染色体过早分离。

DOI:
10.1002/jcp.29612
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发表时间:
2020-02-06
影响因子:
5.6
通讯作者:
Qian, Wei-Ping
Qian, Wei-Ping
中科院分区:
生物学2区
文献类型:
--
作者:
Li, Jian;Dong, Feng;Qian, Wei-Ping

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哺乳动物细胞周期蛋白A1在雄性小鼠的睾丸中表达显著,是减数分裂所必需的,而在卵巢中表达较弱,尤其是在卵母细胞成熟过程中。为了理解为什么细胞周期蛋白A1在卵母细胞中以这种方式表现,我们研究了细胞周期蛋白A1过表达对小鼠卵母细胞减数分裂成熟的影响。我们的研究结果表明,细胞周期蛋白A1过表达触发减数分裂恢复,即使在存在的germinal囊泡破裂抑制剂,米力农。然而,cyclin A1过表达的卵母细胞不能排出第一极体,而是完全停滞在中期I。因此,细胞周期蛋白A1过表达破坏纺锤体形态和染色体排列诱导过早分离的染色体和姐妹染色单体。因此,细胞周期蛋白A1过表达虽然可以促进减数分裂的恢复,但会阻止卵母细胞的成熟。这些结果表明,卵母细胞中cyclin A1表达的降低可能对维持卵母细胞减数分裂成熟过程中持续的前期阻滞和染色体有序分离具有进化意义。
Mammalian cyclin A1 is prominently expressed in testis and essential for meiosis in the male mouse, however, it shows weak expression in ovary, especially during oocyte maturation. To understand why cyclin A1 behaves in this way in the oocyte, we investigated the effect of cyclin A1 overexpression on mouse oocyte meiotic maturation. Our results revealed that cyclin A1 overexpression triggered meiotic resumption even in the presence of germinal vesicle breakdown inhibitor, milrinone. Nevertheless, the cyclin A1-overexpressed oocytes failed to extrude the first polar body but were completely arrested at metaphase I. Consequently, cyclin A1 overexpression destroyed the spindle morphology and chromosome alignment by inducing premature separation of chromosomes and sister chromatids. Therefore, cyclin A1 overexpression will prevent oocyte maturation although it can promote meiotic resumption. All these results show that decreased expression of cyclin A1 in oocytes may have an evolutional significance to keep long-lasting prophase arrest and orderly chromosome separation during oocyte meiotic maturation.