The Demethylating Agent 5-Aza-2 '-Deoxycytidine (5-AZA-CdR) Inhibits The Development of Preimplantation Mouse Embryos

文献类型： 外文期刊

第一作者： Yu Jian-Ning

作者： Yu Jian-Ning;Li Shao-Hua;Wang Dan-Qiu;Wang Meng;Lin Fen;Liu Hong-Lin;Yu Jian-Ning

作者机构：

关键词： 5-AZA-CdR;apoptosis;development;DNA methylation;transcriptional activity

期刊名称：PROGRESS IN BIOCHEMISTRY AND BIOPHYSICS （ 影响因子：0.351； 五年影响因子：0.272 ）

ISSN： 1000-3282

年卷期： 2009 年 36 卷 2 期

页码：

收录情况： SCI

摘要： DNA methylation is crucial for mammalian development, and DNA methylation is always in the dynamic status during preimplantation mouse embryos development. The effects of 5-A-ZA-CdR on the development of preimplantation mouse embryos were evaluated. Preimplantation mouse embryos created by in vitro fertilization were cultured continuously in 5-AZA-CdR (0.2, 1.0, or 5.0 mu mol/L). Fertilized oocytes exposed to CZB containing 5-A-ZA-CdR at the pronuclear stage were unable to form morulae (0.2 and 1.0 mu mol/L) or 4-cell embryos (5.0 mu mol/L), while 2-cell stage embryos exposed to 5-AZA-CdR developed into uncompacted 8-cell (0.2 and 1.0 mu mol/L) or 3/4-cell (5.0 mu mol/L) stage embryos. The rate of morula formation was significantly lower in 4-cell embryos cultured in 5-AZA-CdR (1.0 or 5.0 mu mol/L) than that in control embryos (P < 0.05). These data indicate that 5-A-ZA-CdR inhibits the development of mouse preimplantation embryos. Apoptosis, DNA methylation, and transcriptional activity were analyzed to determine the reason for these developmental defects. An annexin V-PI assay revealed that high doses of 5-AZA-CdR led to apoptosis. Compared to the controls, DNA methylation was significantly reduced in uncompacted 8-cell embryos and morulae (P < 0.05) in a dose-dependent manner, whereas no significant change was detected in 2- or 4-cell embryos (P > 0.05). The observed changes in transcriptional activity, determined by measuring the incorporation of BrUTP, were similar to the observed alterations in DNA methylation. Therefore, the developmental defects induced by 5-AZA-CdR appear to be mediated by alterations in DNA methylation and transcriptional activity in preimplantation mouse embryos.

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