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In utero exposure to diesel exhaust particulates is associated with an altered cardiac transcriptional response to transverse aortic constriction and altered DNA methylation.

ABSTRACT: In utero exposure to diesel exhaust particulates has been associated with increased adult susceptibility to heart failure in mice but the mechanisms by which this exposure promotes susceptibility are poorly understood. To identify potential transcriptional effects that mediate this susceptibility, we have performed RNA-seq analysis on adult hearts from mice exposed to diesel exhaust in utero and that have subsequently undergone transverse aortic constriction. We identified three target genes, Mir133a-2, Ptprf and Pamr1, which demonstrate dysregulation after exposure and aortic constriction. Examination of expression patterns in human heart tissue indicate a correlation between expression and heart failure. We subsequently examined for DNA methylation modifications at these candidate loci in neonatal cultured cardiac myocytes after in utero exposure to diesel exhaust and found that the promoter for Mir133a-2 is differentially methylated.

ORGANISM(S): Mus musculus

PROVIDER: GSE91398 | GEO | 2017/11/27

SECONDARY ACCESSION(S): PRJNA356940

REPOSITORIES: GEO

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Project description:There is an emerging concern that particulate air pollution increases the risk of cranial nerve disease onset. Small nanoparticles, mainly derived from diesel exhaust particles reach the olfactory bulb by their nasal depositions. It has been reported that diesel exhaust inhalation causes inflammation of the olfactory bulb and other brain regions. However, these toxicological studies have not evaluated animal rearing environment. We hypothesized that rearing environment can change mice phenotypes and thus might alter toxicological study results. In this study, we exposed mice to diesel exhaust inhalation at 90 micro g/m3, 8 hours/day, for 28 consecutive days after rearing in a standard cage or environmental enrichment conditions. Microarray analysis found that expression levels of 112 genes were changed by diesel exhaust inhalation. Functional analysis using Gene Ontology revealed that the dysregulated genes were involved in inflammation and immune response. This result was supported by pathway analysis. Quantitative RT-PCR analysis confirmed 10 genes. Interestingly, background gene expression of the olfactory bulb of mice reared in a standard cage environment was changed by diesel exhaust inhalation, whereas there was no significant effect of diesel exhaust exposure on gene expression levels of mice reared with environmental enrichment. The results indicate for the first time that the effect of diesel exhaust exposure on gene expression of the olfactory bulb was influenced by rearing environment. Rearing environment, such as environmental enrichment, may be an important contributive factor to causation in evaluating still undefined toxic environmental substances such as diesel exhaust. RNA sample was taken from olfactory bulb of 56-day-old mouse received diesel exhaust (DE) inhalation at 90 micro g/m3, 8 hours/day, for 28 consecutive days, while control RNA was taken from mouse received clean air, after rearing in a standard cage or environmental enrichment conditions. Comparisons among groups were made by one-color method with normalized data from Cy3 channels for data analysis.

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In utero exposure to diesel exhaust particulates is associated with an altered cardiac transcriptional response to transverse aortic constriction and altered DNA methylation.

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