Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

In utero allergen exposure reprograms primary developmental patterns of lung gene expression and influences respiratory phenotype in rat models of asthma susceptibility.

ABSTRACT: Transcriptome of whole lung of rat from 3 genetic strains, 3 postnatal time points and 2 exposures (saline versus ovalbumin) in (mainly) 4 replicate measurements per condition. Total RNA obtained from whole lung of rat from 3 genetic strains, 3 postnatal time points and 2 exposures (saline versus ovalbumin) in (mainly) 4 replicate measurements per condition.

ORGANISM(S): Rattus norvegicus

SUBMITTER: Alvin Kho

PROVIDER: E-GEOD-32622 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Maternal allergen exposure reprograms the developmental lung transcriptome in atopic and normoresponsive rat pups.

Carpe Nicole N Mandeville Isabel I Kho Alvin T AT Qiu Weiliang W Martin James G JG Tantisira Kelan G KG Raby Benjamin A BA Weiss Scott T ST Kaplan Feige F

American journal of physiology. Lung cellular and molecular physiology 20120914 10

The "fetal origins hypothesis" argued that physiological changes consequent to in utero exposures ultimately contribute to disease susceptibility in later life. The dramatic increase in asthma prevalence is attributed to early exposures acting on preexisting asthma-susceptible genotypes. We showed previously that distinct transcriptome signatures distinguish the developmental respiratory phenotype of atopic (Brown Norway, BN) and normoresponsive (Lewis) rats. We aimed to determine whether matern ...[more]

PMID: 22983352

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Project description:Occupational exposure to crystalline silica results in serious health effects, most notably, silicosis and cancer. A proper understanding of the mechanism(s) underlying the initiation and progression of silica-induced pulmonary toxicity is critical for the intervention and/or prevention of the adverse health effects associated with crystalline silica exposure. Rats were exposed to crystalline silica by inhalation at a concentration of 15 mg/m3, 6 hours/day, 5 days/week for 3, 6 or 12 weeks. At the end of each exposure time point, toxicity and global gene expression changes were determined in the lungs. In general, silica exposure resulted in pulmonary toxicity that was dependent on the duration of silica exposure. A significant and silica exposure time-dependent increase in lactate dehydrogenase activity and accumulation of alveolar macrophages and infiltrating neutrophils in the bronchoalveolar lavage fluid suggested crystalline silica-induced pulmonary toxicity in the rats. Histological changes indicative of pulmonary toxicity were detectable only in the lungs of rats that were exposed to silica for 6- or 12-weeks. Minimal, sub-acute pulmonary inflammation consisting mainly of macrophage accumulation and infiltration of neutrophils was seen in 2 out of 8 rats in the 6-week silica exposure group. Chronic active inflammation, type II pneumocyte hyperplasia, and fibrosis were detected following 12-weeks of silica exposure in all rat lungs. In addition, crystalline silica was visible in the lungs of the rats belonging to the 12-week exposure group. A significant increase in the number of neutrophils seen in the blood indicated silica-induced systemic inflammation in the rats. Microarray analysis of the global gene expression profiles of the rat lungs detected significant differential expression (FDR p <0.05 and fold change >1.5) of 38, 77 and 99 genes in the rats exposed to silica for 3-, 6- and 12-weeks, respectively, compared to the time-matched controls. Bioinformatics analysis of the differentially expressed genes identified significant enrichment of functions, networks and pathways related to inflammation, cancer, oxidative stress, fibrosis and tissue remodeling in the lungs of the silica exposed rats. Collectively, the results of our study provided insights into the molecular mechanisms underlying pulmonary toxicity following sub-chronic exposure to silica in rats. 36 samples were analyzed in this experiment. 6 rats were exposed to crystalline silica by inhalation 15 mg/m3, 6 hours/day, 5 days, 3 weeks. 6 rats were exposed to crystalline silica by inhalation 15 mg/m3, 6 hours/day, 5 days, 6 weeks. 6 rats were exposed to crystalline silica by inhalation 15 mg/m3, 6 hours/day, 5 days, 12 weeks. 18 rats served as controls (6 for each 3 week, 6 week, and 12 week exposure) and were exposed to air during treatment times. Lung gene expression profiling was performed using RNA isolated from rat lung samples.

Dataset Information

In utero allergen exposure reprograms primary developmental patterns of lung gene expression and influences respiratory phenotype in rat models of asthma susceptibility.

Publications

Maternal allergen exposure reprograms the developmental lung transcriptome in atopic and normoresponsive rat pups.

Similar Datasets

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