期刊
REPRODUCTIVE TOXICOLOGY
卷 67, 期 -, 页码 85-99出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.reprotox.2016.11.016
关键词
5-Aza-2 '-deoxycytidine; Embryo; DNA methylation; Cleft palate; Apoptosis; Proliferation
资金
- Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health [P20GM103453]
- NIH grants [HD053509, DE018215, DE021460]
- EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT [R01HD053509] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR RESEARCH RESOURCES [P20RR017702] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH [R03DE021460] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DENTAL &CRANIOFACIAL RESEARCH [R01DE018215] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [P20GM103453] Funding Source: NIH RePORTER
In this study, we identify gene targets and cellular events mediating the teratogenic action(s) of 5-Aza-2'-deoxycytidine (AzaD), an inhibitor of DNA methylation, on secondary palate development. Exposure of pregnant mice (on gestation day (GD) 9.5) to AzaD for 12 h resulted in the complete penetrance of cleft palate (CP) in fetuses. Analysis of cells of the embryonic first branchial arch (1-BA), in fetuses exposed to AzaD, revealed: 1) significant alteration in expression of genes encoding several morphogenetic factors, cell cycle inhibitors and regulators of apoptosis; 2) a decrease in cell proliferation; and, 3) an increase in apoptosis. Pyrosequencing of selected genes, displaying pronounced differential expression in AzaD-exposed 1-BAs, failed to reveal significant alterations in CpG methylation levels in their putative promoters or gene bodies. CpG methylation analysis suggested that the effects of AzaD on gene expression were likely indirect. (C) 2016 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据