哺乳动物卵母细胞非整倍体产生机制的研究进展

doi:10.16431/j.cnki.1671-7236.2021.11.021

摘要/Abstract

摘要： 雌性生殖细胞进行减数分裂时易发生染色体分离错误而产生非整倍体卵母细胞，其受精后会产生非整倍体胚胎，导致出生缺陷或胚胎致死，是影响哺乳动物繁殖的重要因素。卵母细胞在第一次减数分裂前期发生同源染色体联会，此时DNA双链断裂引发重组。重组时缺乏交叉、重组事件数量的减少及交叉靠近端粒或着丝粒导致染色体发生同向分离或不分离，从而产生非整倍体卵母细胞。减数分裂期间，当染色体的端粒共向于同一极或没有完全附着在纺锤体微管上时，纺锤体组装检查点（spindle assembly checkpoint，SAC）被激活，E3泛素连接酶APC/Cyclome （APC/C）沉默，保护分离酶抑制蛋白（securin）和细胞周期蛋白B （cyclin B）不被降解，从而抑制分离酶和染色体的分离。直到所有染色体与纺锤体实现稳定的双极定向并正确排列到赤道板上，SAC关闭，染色体正确分离。卵母细胞中SAC蛋白缺失，导致SAC不能有效地监测端粒在纺锤体上的正确附着，发生染色体分离错误，从而产生非整倍体卵母细胞。因此，通过现代分子技术手段解析非整倍体卵母细胞所涉及的机制是保护哺乳动物生育的重要目标。作者主要介绍了卵母细胞减数分裂的特点，详细阐述了卵母细胞非整倍体发生的染色体分离错误的分子机制，以期为开发卵母细胞非整倍体的治疗手段提供参考。

关键词: 卵母细胞; 减数分裂; 非整倍体; 重组; 纺锤体组装检查点(SAC)

Abstract: During meiosis, the female germ cells are prone to chromosomal separation errors, resulting in aneuploid oocytes. After fertilization, aneuploid embryos will be produced, resulting in birth defects or embryo death, which is an important factor affecting mammalian reproduction. Homologous chromosome synapsis occurs in oocytes at the early stage of the first meiosis, when DNA double strand breaks trigger recombination. The lack of crossover during recombination, the reduction of the number of recombination events and the proximity of crossover to telomeres or centromeres lead to co-oriented segregation or no segregation of chromosomes, then bringing about aneuploid oocytes. During meiosis, when there is an error in the connection between the chromosome kinetochore and the spindle microtuble, the spindle assembly checkpoint (spindle assembly checkpoint, SAC) is activated, the E3 ubiquitin ligase APC/Cyclome (APC/C) is silenced, and the APC targeting proteins securin and cyclin B are protected from degradation, thus inhibiting the separase and the continued separation of chromosomes. Until all chromosomes and spindles achieve stable bipolar orientation and are correctly arranged on the equatorial plate, SAC is closed and chromosomes are separated correctly. The absence of SAC protein in oocytes leads to SAC unable to effectively monitor the correct attachment of telomeres to the spindle, resulting in chromosome segregation errors and aneuploid oocytes. Therefore, analyzing the mechanism involved in aneuploid oocytes by modern molecular technology is an important goal to protect mammalian fertility. This article mainly introduced the characteristics of oocyte meiosis, and expounded in detail the molecular mechanism of chromosome segregation error in oocyte aneuploidy, in order to provide reference for the development of treatment methods for aneuploid oocytes.

Key words: oocyte; meiosis; aneuploidy; recombination; spindle assembly checkpoint (SAC)

中图分类号:

Q952

刘理想, 赵向远, 邵静, 范冰峰, 韩玉萍, 杨镒峰, 许保增. 哺乳动物卵母细胞非整倍体产生机制的研究进展[J]. 中国畜牧兽医, 2021, 48(11): 4115-4124.

LIU Lixiang, ZHAO Xiangyuan, SHAO Jing, FAN Bingfeng, HAN Yuping, YANG Yifeng, XU Baozeng. Advances in Mechanism of Aneuploidy in Mammalian Oocytes[J]. China Animal Husbandry and Veterinary Medicine, 2021, 48(11): 4115-4124.

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