“生存还是毁灭”,发育还是阻滞──小鼠早胚体外发育2-细胞阻滞产生机制初析  

To be or not to be", to develop or to be blocked ──The mechanism of 2-cell block in the early mouse embryo cultured in vitro

作　　者：邱佳菁[1] 李逸平[1] 

机构地区：[1]中国科学院上海细胞生物学研究所,上海200031

出　　处：《生命科学》2000年第5期193-198,共6页Chinese Bulletin of Life Sciences

基　　金：国家自然科学基金!(39870379)

摘　　要：在体外培养条件下，小鼠受精卵往往经一次分裂后就停滞在２－细胞期，不能完成到达囊胚的后续发育过程；称作２－细胞阻滞。氧自由基伤害、培养液成分不平衡等外界因素都能引起阻滞。小鼠的２－细胞阻滞现象受细胞质内母型物质制约，具有品系依赖性。在阻滞品系小鼠胚胎的细胞质内可能缺乏某些重要的蛋白因子，在无外源信号的培养体系内不能继续分裂。发生阻滞的胚胎细胞内ＭＰＦ前体物虽然储备充足，但因无法去磷酸化激活而最终导致发育阻滞。阻滞发生的时间同合子型基因激活（ＺＧＡ）开启的时间刚好相吻合，而在２－细胞阻滞的胚胎中，ＺＧＡ未开启。总之，体外培养环境的不利影响、外源信号的丧失及胚胎细胞质内母型蛋白质的匮乏都阻碍了合子钟对 ＺＧＡ的正常调控。而 ＭＰＦ的正常激活则是 ＺＧＡ后的下游事件。所以 ＺＧＡ不能开启很可能是导致 ２－细胞阻滞的关键原因。When mouse embryos are cultured from 1-cell stage in vitro, they generally fail to undergo a second cleavage and are arrested at 2-cell stage, which is know as the "2-cell block". Abnormal conditions in the cultural medium such as oxygen-free radical damage and environment imbalance may cause block. The phenomenon of "2-cell block" is strain dependent, and is maternally restricted by cytoplasm. Deficiency in the cytoplasm of some important proteins and absence of external signals from the cultural medium are also two of the reasons for 2-cell block. Mouse embryos arrested at 2-cell stage contain sufficient amount of inactive pre-MPF. The cleavage is inhibited by the inability to dephosphorylate and activate pre-MPF in the second cell cycle. Suppression of initial zygotic gene activation (ZGA) induction is involved in the 2-cell block of mouse embryos in vitro. The critical period for 2-cell stage arrest correlates with the initial phase of ZGA. Normal regulation of ZGA by zygotic clock may be prevented because of unfavourable environment, absence of external signals and deficiency of some important proteins in the cytoplasm. And the activation of MPF is the downstream event of ZGA. In summary, the block of early development is mainly due to the failure of ZGA in cultured embryos.

关 键 词：哺乳动物 胚胎发育 2-细胞阻滞 母型限制 ZGA 

分 类 号：Q954.4[生物学—动物学] Q132.4