Ethanol exposure induces differential microRNA and target gene expression and teratogenic effects which can be suppressed by folic acid supplementation.
نویسندگان
چکیده
BACKGROUND 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. METHODS 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. RESULTS 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). CONCLUSIONS The study provided new insights into the role of miRNAs and their target genes in the pathogenesis of fetal alcohol syndrome.
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ورودعنوان ژورنال:
- Human reproduction
دوره 24 3 شماره
صفحات -
تاریخ انتشار 2009