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

电子尼古丁输送装置（ENDS），包括电子烟（e-cigs）和JUUL型装置，于2007年引入美国市场。从电子烟vaping到现在的“JUULing”，ENDS的前景正在迅速发展，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，母亲吸烟的比例与母亲吸烟的比例相似。然而，吸入ENDS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，在子宫内暴露于第三代电子烟气雾剂的小鼠在出生时的身长和体重都较小。还观察到肺结构改变和Wnt信号通路下调，表明子宫内电子烟暴露延迟了肺发育。然而，关于子宫内JUUL气溶胶暴露（含有50 mg/ml尼古丁盐和苯甲酸）影响肺发育的表观遗传和分子机制的信息不足。在本提案中，我们打算研究母胎相互作用的潜在机制，导致宫内JUUL气溶胶暴露后代的肺部发育受阻。总体而言，该提案旨在1）确定母体“JUULing”引起的影响妊娠结局的母胎免疫毒理学反应改变;和2）评价子宫内JUUL气溶胶暴露在1天、4周龄和8周龄的小鼠中诱导的肺毒性，以评估对出生时、出生后肺泡化后肺发育的影响，以及暴露于室内尘螨过敏原之后。 这项研究将为未来针对孕妇和发育脆弱人群的JUUL产品的法规提供科学依据。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ENDS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.