Maternal NO2 exposure disturbs the long noncoding RNA expression profile in the lungs of offspring in time-series patterns

Gestation is a sensitive window to nitrogen dioxide (NO2) exposure, which may disturb fetal lung development and lung function later in life. Animal and epidemiological studies indicated that long noncoding RNAs (lncRNAs) participate in abnormal lung development induced by environmental pollutant exposure. In the present study, pregnant C57BL/6J mice were exposed to 2.5 ppm NO2 (mimicking indoor occupational exposure) or clean air, and lncRNAs expression profiles in the lungs of offspring mice were determined by lncRNA-seq on embryonic day 13.5 (E13.5), E18.5, postnatal day 1 (P1), and P14. The lung histopathology examination of offspring was performed, followed by weighted gene coexpression network analysis (WGCNA), prediction of lncRNAs-target genes, and the biological processes enrichment analysis of lncRNAs. Our results indicated that maternal NO2 exposure induced hypoalveolarization on P14 and differentially expressed lncRNAs showed a time -series pattern. Following WGCNA and enrichment analysis, 2 modules participated in development-related pathways. Importantly, the expressions of related genes were altered, some of which were confirmed to be related to abnormal vascular development and even lung diseases. The research points out that the maternal NO2 exposure leads to abnormal lung development in offspring that might be related to altered lncRNAs expression profiles with time-series-pattern.

Automated summary

Gestation period is a critical time for nitrogen dioxide (NO2) exposure, which can disrupt fetal lung development and lead to lung function abnormalities later in life. This study found that long noncoding RNAs (lncRNAs) play a role in abnormal lung development caused by environmental pollutant exposure. Maternal exposure to NO2 was shown to induce hypoalveolarization in offspring at P14, and differentially expressed lncRNAs showed a time-series pattern. Gene coexpression network analysis revealed two modules that are involved in development-related pathways. Importantly, the expression of related genes was altered and some were associated with abnormal vascular development and lung diseases.