Effects of nicotine salt-rich JUUL aerosols on the mouse developing lung

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Electronic nicotine delivery devices (ENDS), including electronic-cigarettes (e-cigs) and JUUL-type devices, were introduced to the US market in 2007. From e-cig vaping and now to 'JUULing', the ENDS landscape is evolving quickly to satisfy users' recreational and smoking aid cessation needs. In the US, more than 10% of women smoke during their pregnancy and recent surveys show that rates of maternal vaping is similar to those of maternal smoking. However, the effects of inhaling ENDS aerosol on the health of both mothers and fetuses are largely unknown. We recently showed that mice exposed in utero to third-generation e-cig aerosols had smaller body length and weight at birth. Altered lung structure and down-regulated Wnt signaling pathway were also observed, suggesting that in utero e-cig exposures delayed lung development. Yet, there is insufficient information regarding the epigenetic and molecular mechanisms by which in utero JUUL aerosol exposures, containing 50 mg/ml of nicotine salt and benzoic acid, affect lung development. In this proposal, we intend to investigate the mechanisms underlying the maternal-fetal interactions, leading to impeded lung development in the in utero JUUL aerosolexposed offspring. Overall, this proposal aims at 1) identifying the altered maternal-fetal immunotoxicological responses caused by maternal 'JUULing' that are affecting the pregnancy outcomes; and 2) evaluating the pulmonary toxicity induced by in utero JUUL aerosol exposures in mice at 1 day, plus at 4 and 8 weeks of age, to assess the effects on lung development at birth, after post-natal alveolarization, and following exposures to housedust mite allergens. This study will provide scientific evidence for future regulations on JUUL products for pregnant women and developmentally vulnerable populations. This will also help better inform the healthcare providers and the 10% of women who use ENDS during pregnancy.