Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA.
Department of Environmental Toxicology, Southern University and A & M College, Baton Rouge, LA 70813, USA.
Int J Environ Res Public Health. 2023 Feb 20;20(4):3710. doi: 10.3390/ijerph20043710.
Currently, approximately 8 million adult Americans use electronic cigarettes (e-cigs) daily, including women of childbearing age. It is known that more than 10% of women smoke during their pregnancy, and recent surveys show that rates of maternal vaping are similar to rates of maternal cigarette smoking. However, the effects of inhaling e-cig aerosol on the health of fetuses remain unknown. The objective of the present study was to increase our understanding of the molecular effects caused by in utero exposures to e-cig aerosols on developing mouse lungs and, later in life, on the offspring's susceptibility to developing asthma.
Pregnant mice were exposed throughout gestation to either filtered air or vanilla-flavored e-cig aerosols containing 18 mg/mL of nicotine. Male and female exposed mouse offspring were sacrificed at birth, and then the lung transcriptome was evaluated. Additionally, once sub-groups of male offspring mice reached 4 weeks of age, they were challenged with house dust mites (HDMs) for 3 weeks to assess asthmatic responses.
The lung transcriptomic responses of the mouse offspring at birth showed that in utero vanilla-flavored e-cig aerosol exposure significantly regulated 88 genes in males (62 genes were up-regulated and 26 genes were down-regulated), and 65 genes were significantly regulated in females (17 genes were up-regulated and 48 genes were down-regulated). Gene network analyses revealed that in utero e-cig aerosol exposure affected canonical pathways associated with CD28 signaling in T helper cells, the role of NFAT in the regulation of immune responses, and phospholipase C signaling in males, whereas the dysregulated genes in the female offspring were associated with NRF2-mediated oxidative stress responses. Moreover, we found that in utero exposures to vanilla-flavored e-cig aerosol exacerbated HDM-induced asthma in 7-week-old male mouse offspring compared to respective in utero air + HDM controls.
Overall, these data demonstrate that in utero e-cig aerosol exposure alters the developing mouse lung transcriptome at birth in a sex-specific manner and provide evidence that the inhalation of e-cig aerosols is detrimental to the respiratory health of offspring by increasing the offspring' susceptibility to developing lung diseases later in life.
目前，约有 800 万美国成年人每天使用电子烟（e-cigs），其中包括育龄妇女。已知超过 10%的孕妇吸烟，最近的调查显示，孕妇蒸气的比例与孕妇吸烟的比例相似。然而，吸入电子烟气溶胶对胎儿健康的影响尚不清楚。本研究的目的是增加我们对子宫内暴露于电子烟气溶胶对发育中的小鼠肺部的分子影响的理解，以及对后代易患哮喘的影响。
怀孕的老鼠在整个妊娠期都暴露在过滤空气中或香草味的电子烟气溶胶中，其中含有 18 毫克/毫升的尼古丁。暴露于电子烟的雄性和雌性老鼠后代在出生时被处死，然后评估其肺部转录组。此外，一旦雄性后代老鼠的亚组达到 4 周龄，它们就会用屋尘螨（HDMs）进行 3 周的挑战，以评估哮喘反应。
出生时的老鼠后代的肺部转录组反应表明，子宫内香草味电子烟气溶胶暴露显著调节了雄性的 88 个基因（62 个基因上调，26 个基因下调），而雌性的 65 个基因显著调节（17 个基因上调，48 个基因下调）。基因网络分析表明，子宫内电子烟气溶胶暴露影响了与 T 辅助细胞中 CD28 信号、NFAT 在免疫反应调节中的作用以及雄性中的磷脂酶 C 信号相关的经典途径，而雌性后代中失调的基因与 NRF2 介导的氧化应激反应有关。此外，我们发现，与各自的子宫内空气+HDM 对照组相比，子宫内暴露于香草味电子烟气溶胶会使 7 周龄雄性老鼠后代对 HDM 诱导的哮喘加剧。
总的来说，这些数据表明，子宫内电子烟气溶胶暴露以性别特异性的方式改变了出生时发育中的老鼠肺部转录组，并提供了证据表明，吸入电子烟气溶胶会通过增加后代在以后的生活中患肺部疾病的易感性，对后代的呼吸道健康造成损害。
