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5-AZA-2 '-deoxycytidine (5-AZA-CdR) leads to down-regulation of Dnmt1o and gene expression in preimplantation mouse embryos

文献类型： 外文期刊

作者： Yu, Jian-Ning 1 ; Xue, Chun-Yang 1 ; Wang, Xu-Guang 1 ; Lin, Fei 1 ; Liu, Chun-Yi 1 ; Lu, Fu-Zeng 1 ; Liu, Hong-Lin 1 ;

作者机构： 1.Nanjing Agr Univ, Coll Anim Sci & Technol, Nanjing 210095, Jiangsu, Peoples R China

2.Jiangsu Acad Agr Sci, Inst Anim Sci, Nanjing, Jiangsu, Peoples R China

关键词： 5-AZA-CdR;DNA methylation;Dnmt1o;Gene expression;Preimplantation mouse embryos

期刊名称：ZYGOTE （ 影响因子：1.442； 五年影响因子：1.536 ）

ISSN： 0967-1994

年卷期： 2009 年 17 卷 2 期

页码：

收录情况： SCI

摘要： 5-AZA-2'-deoxycytidine (5-AZA-CdR) is a demethylating, teratogenic agent and a mutagen, which causes defects in the developing mouse and rat after implantation. Our previous data indicated that 5-AZA-CdR (0.2 and 1.0 mu M) inhibited the development of mouse preimplantation embryos. Pronuclear embryos exposed to 5-AZA-CdR at the pronuclear stage were unable to form 8-cell embryos, while 2-cell-stage embryos exposed to 5-AZA-CdR only developed into uncompacted 8-cell-stage embryos. And there was no formation of blastocysts when 4-cell embryos cultured in 5-AZA-CdR. In our present study, we detected Dnmt1o protein and some developmental gene expression in order to find the reasons for the developmental arrest. Dnmt1o could not traffic to 8-cell nuclei as control when embryos were exposed to 5-AZA-CdR. Dnmt1o was in cytoplasm at 2-cell and 4-cell stages before and after treated with 5-AZA-CdR. Gene expression changes were also detected in this research. Our data indicated that connexin 31 (Cx31), connexin 43 (Cx43), connexin 45 (Cx45), E-cadherin (Cdh1) and beta-catenin (Ctnnb1) were all downregulated by 5-AZA-CdR. Cx31, Cx43 and Cx45 are members of connexins family, which have a central role in gap junctions. Cdh1 and Ctnnb1 are necessary for the foundation of tight junctions. Therefore, developmental arrest induced by 5-AZA-CdR may be caused by the failure of Dnmt1o cytoplasmic-nuclear traffic and the down-regulation of developmental gene expression. Normal compaction and blastocoel cavitation need Dnmt1o traffic to 8-cell nuclei and the right gene expression, especially the correlative genes in gap junctions and tight junctions.

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