Expression data from short-term mouse embryonic stem cell exposure Assay
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE57639 | GEO | 2015/12/01
SECONDARY ACCESSION(S): PRJNA247388
REPOSITORIES: GEO
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Project description:Valproic acid (VPA) is a potent inducer of neural tube defects (ntd:s) in both human and mouse, but its mechanism of teratogenicity is not know. The mouse embryonic stem cell line R1, may be relevant as an in vitro model of teratogenicity and was evaluated with exposures to VPA,and the two VPA anlogs (S)-2-pentyl-4-pentynoic acid, and 2-ethyl-4-methyl-pentanoic acid to profile the gene expression response. Those profiles may reveal biomarkers of teratogenic exposures in an in vitro system as well as give mechanistic input of the teratogenicity of VPA.
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Project description:Congenital malformations are a prevalent cause of infant mortality in the United States and their induction has been linked to a variety of factors, including exposure to teratogens. However, the molecular mechanisms of teratogenicity are not fully understood. MicroRNAs are an important group of small, non-coding RNAs that regulate mRNA expression. MicroRNA roles in early embryonic development are well established, and their disruption during development can cause abnormalities. We hypothesized that developmental exposure to teratogens such as valproic acid alters microRNA expression profiles in developing embryos. Valproic acid is an anticonvulsant and mood-stabilizing drug used to treat epilepsy, bipolar disorder and migraines. To examine the effects of valproic acid on microRNA expression during development, we used zebrafish embryos as a model vertebrate developmental system. Zebrafish embryos were continuously exposed to valproic acid (1 mM) or vehicle control (ethanol) starting from 4 hours post-fertilization (hpf) and sampled at 48 and 96 hpf to determine the miRNA expression profiles prior to and after the onset of developmental defects. At 96 hpf, 95% of the larvae showed skeletal deformities, abnormal swimming behavior, and pericardial effusion. Microarray expression profiling was done using Agilent zebrafish miRNA microarrays. Microarray results revealed changes in miRNA expression at both the time points. Thirteen miRNAs were differentially expressed at 48 hpf and 22 miRNAs were altered at 96 hpf. Among them, six miRNAs (miR-16a, 18c, 122, 132, 457b, and 724) were common to both time points. Bioinformatic target prediction and examination of published literature revealed that these miRNAs target several genes involved in the normal functioning of the central nervous system. These results suggest that the teratogenic effects of valproic acid could involve altered miRNA expression. Small RNA profiles were deteremined in valproic acid exposed zebrafish embryos using Agilent miRNA microarrays
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