Differentially expressed genes in the lungs of fetuses mice exposed to ambient air pollution

Introduction - Epidemiologic studies indicate that air pollution affects lung health in prenatal and early childhood. However, the mechanisms involved remain unknown. Aims - Investigate the influence of gestational exposure to concentrated ambient particles (CAPs) derived from vehicular emissions on the expression of genes involved in lung development. Methods - Dams were continuously exposed to either filtered air (control group) or CAP (600µg/m 3 /day) from gestational day 5 (intrauterine exposure) until 14 days post conception (dpc), using a Harvard Ambient Particle Concentrator. At the end of the exposures, the total RNA was isolated from the lungs of fetuses at 14 dpc (n=5/group), using the RNeasy Mini kit (Qiagen). Gene expression profiles were investigated with AffymetrixGeneChip® Mouse 2.0 ST Arrays . Enrichment analysis was performed by Funcassociate 2.0. Results- Microarray data analysis revealed that 86 genes, related to embryogenic development, were differentially expressed in the fetal lung tissue of exposed group when compared to the control group. Fifty-two upregulated (e.g. Shh) and 34 downregulated (e.g. Hoxa5) genes. Notably, upregulated genes were involved in G-protein coupled receptor activity (GO:0004930, corrected p-value l0.001). Furthermore, downregulated genes were enriched in genes regulated by the polycomb repressor complex, which contains both EZH2 and Suz12 transcription factors. Conclusions - Exposure to particulate air pollution during intrauterine life affects the regulation of important genes involved in lung development. We speculate that these alterations in gene regulation could be related to abnormal lung development and function observed in previous studies.