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

电子尼古丁输送装置(END)，包括电子烟(e-cigs)和Juul类装置，于2007年被引入美国市场。从电子烟蒸发到现在的JULING，Ends的格局正在迅速演变，以满足用户的娱乐和戒烟需求。在美国，超过10%的女性在怀孕期间吸烟，最近的调查显示，母亲吸烟的比率与母亲吸烟的比率相似。然而，吸入END气雾剂对母亲和胎儿健康的影响在很大程度上是未知的。我们最近发现，在子宫中暴露于第三代e-cig气雾剂的小鼠出生时的身体长度和体重都较小。还观察到肺结构改变和Wnt信号通路下调，这表明在宫内暴露e-cig会延迟肺发育。然而，关于子宫内暴露于含有50毫克/毫升尼古丁盐和苯甲酸的气雾剂影响肺发育的表观遗传学和分子机制的信息不足。在这项建议中，我们打算调查母婴相互作用的潜在机制，导致宫内JUUL气雾剂暴露的后代肺发育受阻。总体而言，这项建议旨在1)确定影响妊娠结局的母婴免疫毒理反应；2)评估宫内JUUL气雾剂暴露对小鼠的肺部毒性，以评估出生时、出生后肺泡形成后以及暴露于室内尘螨变应原后对小鼠肺发育的影响。 这项研究将为未来针对孕妇和发育脆弱人群的JUUL产品的监管提供科学依据。这也将有助于更好地告知医疗保健提供者和10%在怀孕期间使用END的妇女。

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.