Maternal E-Cigarette Exposure in Mice Alters DNA Methylation and Lung Cytokine Expression in Offspring

Abstract

Introduction: E-cigarette usage is increasing, especially among the young, with both the general population and physicians perceiving them as a safe alternative to tobacco smoking. Worryingly, e-cigarettes are commonly used by pregnant women. As nicotine is known to adversely affect children in-utero, we hypothesised that nicotine delivered via e-cigarettes would negatively affect lung development. To test this we developed a mouse model of maternal e-vapour (nicotine and nicotine-free) exposure, and investigated the impact on the growth and lung inflammation in both offspring and mothers. Method: Female Balb/c mice were exposed to e-fluid vapour containing nicotine (E-cig18mg/mL, equivalent to 2 cigarettes/treatment, twice daily,) or nicotine free (E-cig0mg/mL) from 6 weeks prior to mating until pups weaned. Male offspring were studied at postnatal day (P) 1, 20 and at 13 weeks. The mothers were studied when the pups weaned. Results: In the mothers’ lung, e-cigarette exposure with and without nicotine increased the pro-inflammatory cytokines IL-1β, IL-6 and TNF-α. In adult offspring, TNF-α protein levels were increased in both E-cig18 and E-cig0 groups, whilst IL-1β was suppressed. This was accompanied by global changes in DNA methylation. Conclusion: In this study, we found that e-cigarette exposure during pregnancy adversely affected maternal and offspring lung health. As this occurred with both nicotine free and nicotine containing e-vapour the effects are likely due to by-products of vaporisation rather than nicotine.