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在子宫内暴露于电子烟气雾会损害小鼠肺发育过程中的信号转导。

In utero exposures to electronic-cigarette aerosols impair the signaling during mouse lung development.

机构信息

Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana.

Health Research Center, Department of Environmental Toxicology, Southern University and A&M College, Baton Rouge, Louisiana.

出版信息

Am J Physiol Lung Cell Mol Physiol. 2020 Apr 1;318(4):L705-L722. doi: 10.1152/ajplung.00408.2019. Epub 2020 Feb 21.

DOI:10.1152/ajplung.00408.2019
PMID:32083945
Abstract

Currently, more than 9 million American adults, including women of childbearing age, use electronic-cigarettes (e-cigs). Further, the prevalence of maternal vaping now approaching 10% is similar to that of maternal smoking. Little, however, is known about the effects of fetal exposures to nicotine-rich e-cig aerosols on lung development. In this study, we assessed whether in utero exposures to e-cig aerosols compromised lung development in mice. A third-generation e-cig device was used to expose pregnant BALB/c mice by inhalation to 36 mg/mL of nicotine cinnamon-flavored e-cig aerosols for 14-31 days. This included exposures for either 12 days before mating plus during gestation (preconception groups) or only during gestation (prenatal groups). Respective control mice were exposed to filtered air. Subgroups of offspring were euthanized at birth or at 4 wk of age. Compared with respective air-exposed controls, both preconception and prenatal exposures to e-cig aerosols significantly decreased the offspring birth weight and body length. In the preconception group, 7 inflammation-related genes were downregulated, including 4 genes common to both dams and fetuses, denoting an e-cig immunosuppressive effect. Lung morphometry assessments of preconception e-cig-exposed offspring showed a significantly increased tissue fraction at birth. This result was supported by the downregulation of 75 lung genes involved in the signaling, which is essential to lung organogenesis. Thus, our data indicate that maternal vaping impairs pregnancy outcomes, alters fetal lung structure, and dysregulates the signaling. This study provides experimental evidence for future regulations of e-cig products for pregnant women and developmentally vulnerable populations.

摘要

目前,超过 900 万美国成年人,包括育龄妇女,使用电子烟(e-cigs)。此外,目前接近 10%的产妇蒸气使用率与产妇吸烟率相似。然而,人们对胎儿暴露于富含尼古丁的电子烟气溶胶对肺发育的影响知之甚少。在这项研究中,我们评估了胎儿暴露于电子烟气溶胶是否会损害小鼠的肺发育。第三代电子烟装置用于通过吸入将尼古丁肉桂味电子烟气溶胶暴露于怀孕的 BALB/c 小鼠,每天 14-31 天,浓度为 36mg/ml。这包括在交配前和怀孕期间(受孕前组)或仅在怀孕期间(产前组)进行 12 天的暴露。相应的对照小鼠暴露于过滤空气中。子代表的亚组在出生时或 4 周龄时被安乐死。与各自暴露于空气中的对照相比,受孕前和产前暴露于电子烟气溶胶都会显著降低后代的出生体重和体长。在受孕前组中,有 7 个与炎症相关的基因下调,包括母体和胎儿共有的 4 个基因,这表明电子烟具有免疫抑制作用。对受孕前电子烟暴露的后代的肺形态计量学评估显示,出生时组织分数明显增加。这一结果得到了 75 个与信号转导相关的肺基因下调的支持,这对肺器官发生至关重要。因此,我们的数据表明,产妇蒸气会损害妊娠结局,改变胎儿的肺结构,并扰乱信号转导。本研究为未来对孕妇和发育弱势群体的电子烟产品进行监管提供了实验依据。

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