In Utero Environmental Tobacco Smoke Exposure Alters Gene Expression in Lungs of Adult BALB/c Mice

BACKGROUND: In utero environmental tobacco smoke (ETS) exposure exacerbates initial lung responses of adult mice to ovalbumin (OVA), a common allergen in rodent models of allergic asthma. OBJECTIVE: We tested the hypothesis that in utero ETS exposure alters expression of genes (including asthma-related and inflammatory genes) in the lungs of adult mice and that this differential expression is reflected in differential respiratory and immune responses to nontobacco allergens. METHODS: Using Affymetrix Mouse Genome 430 2.0 arrays, we examined gene expression changes in lungs of BALB/c mice exposed to ETS in utero, OVA, or saline aerosol at weeks 7–8, and OVA sensitization and challenge at weeks 11–15. Data sets were filtered by transcript p-value (≤ 0.05), false discovery rate (≤ 0.05), and fold change (≥ 1.5). Differential expression of selected genes was confirmed by polymerase chain reaction (PCR). RESULTS: Genes differentially expressed as a result of in utero ETS exposure are involved in regulation of biological processes (immune response, cell proliferation, apoptosis, cell metabolism) through altered cytoskeleton, adhesion, transcription, and enzyme molecules. A number of genes prominent in lung inflammation were differentially expressed on PCR but did not pass selection criteria for microarray, including arginase (Arg1), chitinases (Chia, Chi3l3, Chi3l4), eotaxins (Ccl11, Ccl24), small proline-rich protein 2a (Sprr2a), and cytokines (Il4, Il6, Il10, Il13, Tnfa) . CONCLUSION: The differential lung gene expression reported here is consistent with previously reported functional changes in lungs of mice exposed in utero to ETS and as adults to the nontobacco allergen OVA.