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Prenatal Exposure to E-Cigarette Aerosols Leads to Sex-dependent Pulmonary Extracellular Matrix Remodeling and Myogenesis in Offspring Mice.
American Journal of Respiratory Cell and Molecular Biology ( IF 5.9 ) Pub Date : 2020-12-01 , DOI: 10.1165/rcmb.2020-0036oc
Qixin Wang 1 , Isaac K Sundar 1 , Jason L Blum 2 , Jill R Ratner 2 , Joseph H Lucas 1 , Tsai-Der Chuang 3 , Ying Wang 3 , Jie Liu 3 , Virender K Rehan 3 , Judith T Zelikoff 2 , Irfan Rahman 1
Affiliation  

Electronic-cigarette (e-cig) vaping is a serious concern, as many pregnant women who vape consider it safe. However, little is known about the harmful effects of prenatal e-cig exposure on adult offspring, especially on extracellular-matrix (ECM) deposition and myogenesis in the lungs of offspring. We evaluated the biochemical and molecular implications of maternal exposure during pregnancy to e-cig aerosols on the adult offspring of both sexes, with a particular focus on pulmonary ECM remodeling and myogenesis. Pregnant CD-1 mice were exposed to e-cig aerosols with or without nicotine, throughout gestation, and lungs were collected from adult male and female offspring. Compared with the air-exposed control group, female mice exposed to e-cig aerosols, with or without nicotine, demonstrated increased lung protein abundance of LEF-1 (lymphoid enhancer–binding factor 1), fibronectin, and E-cadherin, whereas altered E-cadherin and PPARγ (peroxisome proliferator–activated receptor γ) levels were observed only in males exposed to e-cig aerosols with nicotine. Moreover, lipogenic and myogenic mRNAs were dysregulated in adult offspring in a sex-dependent manner. PAI-1 (plasminogen activator inhibitor-1), one of the ECM regulators, was significantly increased in females exposed prenatally to e-cig aerosols with nicotine and in males exposed to e-cig aerosols compared with control animals exposed to air. MMP9 (matrix metalloproteinase 9), a downstream target of PAI-1, was downregulated in both sexes exposed to e-cig aerosols with nicotine. No differences in lung histology were observed among any of the treatment groups. Overall, adult mice exposed prenatally to e-cig aerosols could be predisposed to developing pulmonary disease later in life. Thus, these findings suggest that vaping during pregnancy is unsafe and increases the propensity for later-life interstitial lung diseases.



中文翻译:

产前接触电子烟气溶胶导致后代小鼠的性别依赖性肺细胞外基质重塑和肌生成。

电子烟 (e-cig) vaping 是一个严重的问题,因为许多 vape 的孕妇认为它是安全的。然而,关于产前电子烟暴露对成年后代的有害影响知之甚少,尤其是对后代肺部细胞外基质 (ECM) 沉积和肌生成的有害影响。我们评估了母体在怀孕期间接触电子烟气溶胶对男女成年后代的生化和分子影响,特别关注肺 ECM 重塑和肌生成。怀孕的 CD-1 小鼠在整个妊娠期间暴露于含有或不含尼古丁的电子烟气雾剂中,并从成年雄性和雌性后代收集肺。与暴露于空气的对照组相比,暴露于电子烟气雾剂的雌性小鼠,无论是否含有尼古丁,证明 LEF-1(淋巴增强子结合因子 1)、纤连蛋白和 E-钙粘蛋白的肺蛋白丰度增加,而仅在暴露于 e-含尼古丁的香烟气雾剂。此外,成体后代的脂肪生成和肌生成 mRNA 以性别依赖性方式失调。PAI-1(纤溶酶原激活剂抑制剂-1)是 ECM 调节剂之一,与暴露于空气的对照动物相比,在产前暴露于含有尼古丁的电子烟气雾剂的女性和暴露于电子烟气雾剂的男性中显着增加。MMP9(基质金属蛋白酶 9)是 PAI-1 的下游靶标,在暴露于含有尼古丁的电子烟气溶胶的两性中均被下调。在任何治疗组中均未观察到肺组织学差异。总体,产前暴露于电子烟气溶胶的成年小鼠可能在以后的生活中易患肺部疾病。因此,这些发现表明,在怀孕期间抽电子烟是不安全的,并且会增加晚年间质性肺疾病的倾向。

更新日期:2020-12-01
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