Автор |
Yu, Jian-Ning |
Автор |
Xue, Chun-Yang |
Автор |
Wang, Xu-Guang |
Автор |
Lin, Fei |
Автор |
Liu, Chun-Yi |
Автор |
Lu, Fu-Zeng |
Автор |
Liu, Hong-Lin |
dc.description |
Summary5-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 μM) 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 β-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. |
Формат |
application.pdf |
Издатель |
Cambridge University Press |
Копирайт |
Copyright © Cambridge University Press 2009 |
Тема |
5-AZA-CdR |
Тема |
DNA methylation |
Тема |
Dnmt1o |
Тема |
Gene expression |
Тема |
Preimplantation mouse embryos |
Название |
5-AZA-2′-deoxycytidine (5-AZA-CdR) leads to down-regulation of Dnmt1o and gene expression in preimplantation mouse embryos |
Тип |
research-article |
DOI |
10.1017/S0967199408005169 |
Electronic ISSN |
1469-8730 |
Print ISSN |
0967-1994 |
Журнал |
Zygote |
Том |
17 |
Первая страница |
137 |
Последняя страница |
145 |
Аффилиация |
Yu Jian-Ning; Nanjing Agricultural University; Institute of Animal Science |
Аффилиация |
Xue Chun-Yang; Nanjing Agricultural University |
Аффилиация |
Wang Xu-Guang; Nanjing Agricultural University |
Аффилиация |
Lin Fei; Nanjing Agricultural University |
Аффилиация |
Liu Chun-Yi; Nanjing Agricultural University |
Аффилиация |
Lu Fu-Zeng; Nanjing Agricultural University |
Аффилиация |
Liu Hong-Lin; Nanjing Agriculture University |
Выпуск |
2 |