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Effect of Pre- and Postnatal Exposure to urban PM2.5 on the Transcriptome of the Developing and Early-Life Mouse Lung

ABSTRACT: Over the last years, evidence has grown that exposure to air pollution, in addition to impairing lung function and health in individuals of all age, can be linked to negative effects in newborn when present during pregnancy. Data suggests that intrauterine exposure of fetuses (exposure of the mother to air pollution during pregnancy) in fact exerts a negative impact on lung development. However, the means by which exposure during pregnancy affects lung development, have not been studied in depth yet. In this study, we investigated alterations of the transcriptome of the developing lung in a mouse model of gestational and early-life postnatal exposure to urban PM2.5 (from Sao Paulo, Brazil).

ORGANISM(S): Mus musculus

PROVIDER: GSE104656 | GEO | 2018/06/08

REPOSITORIES: GEO

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Project description:In the present study, we investigate pulmonary transcriptional responses in mice following exposure in situ to ambient air in a heavily polluted urban environment. Mature C57BL/CBA male mice were caged in sheds located in an urban area near two working steel mills and a major highway in Hamilton, Ontario, Canada. Control mice were housed in the same environment but received only high-efficiency particle-filtered air. Whole lung tissues were collected from mice exposed for 3 weeks, 10 weeks or for 10 weeks followed by 6 weeks in the laboratory (16 weeks total). DNA microarrays were used to explore changes in pulmonary gene expression in mice breathing ambient air versus HEPA-filtered air. Transcriptional profiling revealed changes in the expression of genes implicated in the lipid droplet synthesis pathway (plin, dgat2, lpl, s3-12, agpat2), antioxidants (ucp1). We postulate that exposure to particulate matter adsorbed with polycyclic aromatic hydrocarbons triggers lipid droplet synthesis (holding depots for lipids and malformed/excess proteins tagged for degradation) in the lungs, which act to sequester particulates adsorbed with toxic chemicals. Increased lipid droplet synthesis could potentially lead to endogenous/stressor-induced synthesis of reactive oxygen species and activation of antioxidant mechanisms. Further investigation into the stimulation of lipid droplet synthesis in the lung in response to air pollution is warranted in order to better understand these mechanistic changes and the resulting health implications. Mature male C57BL/6 x CBA F1 hybrid mice were exposed to either HEPA-filtered or ambient air in Hamilton, ON, Canada. Animals were exposed starting May 14, 2004 for 3 weeks (3wk), 10 weeks (10wk), or for 10 weeks followed by 6 weeks of recovery (16wk). Each treatment group consisted of five mice, for a total of 30 mice. Total RNA was isolated from a random section of the whole lung using TRIzol reagent (Invitrogen) and purified using the RNeasy Mini Kit (Qiagen). RNA quality was confirmed by UV spectrophotometry and using an Agilent Bioanalyzer. Total RNA (200 ng) from HEPA-filtered air or whole air-exposed mice and Universal Mouse Reference RNA (Stratagene) were used to synthesize double-stranded cDNA and cyanine-labelled cRNA according to the manufacturer's instructions (Agilent Linear Amplification Kits, Agilent Technologies). Biological samples were labelled with Cy5 dye while the commercially available Stratagene mouse reference RNA was labelled with Cy3 dye. At each of the three time points, ambient air-exposed samples and HEPA-filtered samples were hybridized to Agilent microarrays. Arrays were washed, and scanned on an Agilent G2505B scanner. Data were acquired using the Agilent Feature Extraction software version 9.5.3.1.

Project description:Atmospheric particulate matter (PM) is a recognized risk factor for the global burden of disease in human populations. We are presenting here the application of toxicogenomics in the evaluation of the toxic effects of organic content of atmospheric particle matter (PM), from urban and rural environments (city of Barcelona and village of La Pobla, NE Spain), using the developing zebrafish embryo. The main goal is to identify the metabolic pathways involved in the adverse effects observed in zebrafish embryos exposed to PM organic content from urban and rural environments, also allowing the selection of genes of interest that are differentially expressed. The relevance of particle size to the PM toxicity is also addressed. Indeed, the zebrafish embryos were exposed to PM of aerodynamic diameter larger than 7.2 μm and smaller than 0.5 μm (PM10 and PM0.5, respectively). PM0.5 concentrated biological and toxic activities linked to organic substances. Transcriptomic analyses showed strong induction of the AhR signalling pathway (a.k.a. dioxin-like activity) for embryos exposed to both rural and urban extracts, correlating with the concentrations of PAHs. Urban extracts, with strong contribution of traffic emissions, specifically de-regulated oxidative stress-related genes, as well as pancreatic and eye-lens specific genes, two organs known to be affected by air pollution in humans. Exposure to rural extracts, with high contribution of wood burning emissions, affected genes implicated in basic cellular functions, in agreement with their strong embryotoxicity. Extracts from rural and urban samples elicited both common and specific transcriptome responses, suggesting different potentially adverse outcomes depending on PM source and composition. The authors thank the financial support of the Spanish Ministry (project TEA-PARTICLE, grant number CGL2011-29621) and the Portuguese Foundation for Science and Technology for the doctoral grant of Sofia R. Mesquita (SFRH/BD/80710/2011) funded by the Program POPH-QREN through the Portuguese Ministry of Education and Science and the European Social Fund, and support through project PEst-C/MAR/LA0015/2013.

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Effect of Pre- and Postnatal Exposure to urban PM2.5 on the Transcriptome of the Developing and Early-Life Mouse Lung

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