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学科主题: 公共卫生
题名:
Ethanol exposure induces differential microRNA and target gene expression and teratogenic effects which can be suppressed by folic acid supplementation
作者: Wang, Lin-Lin1,2; Zhang, Zhaofeng2; Li, Qiong2; Yang, Ruiyue2; Pei, Xinrong2; Xu, Yajun2; Wang, Junbo2; Zhou, Shu-Feng1; Li, Yong2
关键词: ethanol ; miR-10a ; miR-10b ; birth defects ; Hoxa1
刊名: HUMAN REPRODUCTION
发表日期: 2009-03-01
DOI: 10.1093/humrep/den439
卷: 24, 期:3, 页:562-579
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Obstetrics & Gynecology ; Reproductive Biology
研究领域[WOS]: Obstetrics & Gynecology ; Reproductive Biology
关键词[WOS]: TEMPORAL COLINEARITY ; ALCOHOL EXPOSURE ; EMBRYO CULTURE ; CELL-DEATH ; SMALL RNAS ; HOX GENES ; MOUSE ; MICE ; HINDBRAIN ; TOXICITY
英文摘要:

microRNAs (miRNAs) play an important role in development and are associated with birth defects. Data are scant on the role of miRNAs in birth defects arising from exposure to environmental factors such as alcohol.

In this study, we determined the expression levels of 509 mature miRNAs in fetal mouse brains with or without prenatal ethanol exposure using a miRNA microarray technique, verified by northern blot and PCR. Mouse embryos in culture were used to examine the effect of ethanol treatment on expression of the putative target genes of miR-10a (Hoxa1 and other Hox members) at mRNA and protein level. Open field and Morris water maze tests were also performed at post-natal day 35.

Ethanol treatment induced major fetal teratogenesis in mice and caused mental retardation in their offspring, namely lower locomotor activity (P < 0.01) and impaired task acquisition. Of the screened miRNAs, miR-10a, miR-10b, miR-9, miR-145, miR-30a-3p and miR-152 were up-regulated (fold change > 1.5) in fetal brains with prenatal ethanol exposure, whereas miR-200a, miR-496, miR-296, miR-30e-5p, miR-362, miR-339, miR-29c and miR-154 were down-regulated (fold change < 0.67). Both miR-10a and miR-10b were significantly up-regulated (P < 0.01) in brain after prenatal ethanol exposure. Ethanol treatment also caused major obstruction in the development of cultured embryos, with down-regulated Hoxa1. Co-incubation with folic acid blocked ethanol-induced teratogenesis, with up-regulated Hoxa1 and down-regulated miR-10a (P < 0.01).

The study provided new insights into the role of miRNAs and their target genes in the pathogenesis of fetal alcohol syndrome.

语种: 英语
所属项目编号: 30671760 ; 30271364
项目资助者: National Natural Sciences Foundations of People&prime ; s Republic of China
WOS记录号: WOS:000263827800011
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/62303
Appears in Collections:北京大学公共卫生学院_期刊论文

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作者单位: 1.RMIT Univ, Div Chinese Med, Sch Hlth Sci, WHO Collaborating Ctr Tradit Med, Bundoora, Vic 3083, Australia
2.Peking Univ, Sch Publ Hlth, Dept Food Hyg & Nutr, Beijing 100191, Peoples R China

Recommended Citation:
Wang, Lin-Lin,Zhang, Zhaofeng,Li, Qiong,et al. Ethanol exposure induces differential microRNA and target gene expression and teratogenic effects which can be suppressed by folic acid supplementation[J]. HUMAN REPRODUCTION,2009,24(3):562-579.
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