Prenatal Exposure to Electronic-Cigarette Aerosols Leads to Sex-Dependent Pulmonary Extracellular-Matrix Remodeling and Myogenesis in Offspring Mice

Abstract

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 PPARg (peroxisome proliferator-activated receptor g) 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.

Impact of gestational electronic cigarette vaping on amino acid signature profile in the pregnant mother and the fetus

“…Additionally, the chemical constituents of the aerosols produced by the vaping chamber system were found to resemble the chemical profile of aerosols derived from human e-cig vaping devices [ 20 , 24 , 25 ]. Dams were exposed to the vaping treatment for 3 h per day, 5 days per week from gestation day (GD) 5–20 [ 5 , 20 , 26 ]. Each episode of vaping treatment utilized a commercially available e-cig atomizer (Sense Herakles) that produced a 1 s puff of ~42 mL every 20 s. The e-cig base liquid utilized for the EC-Base group was compounded in-lab with a 80:20 composition ratio of propylene glycol (Fischer) and glycerol (Fischer), respectively.…”

“…Furthermore, there is only a small set of studies examining the short-term effects of e-cig vaping in adult humans. The limited number of animal studies conducted on the effects of e-cig aerosol exposure during pregnancy have established that e-cigs can negatively affect fetal growth, the cardiopulmonary system, and nervous system development [ [4] , [5] , [6] ]. The large knowledge gap on the effects of e-cig vaping necessitates a systematic investigation into how these devices impact pregnancy and development.…”

Molecular clock REV-ERBα regulates cigarette smoke–induced pulmonary inflammation and epithelial-mesenchymal transition

“…The staining protocol has been described in our previous study (51). Lung sections were stained using the Gomori's Trichrome staining kit that was commercially available (Cat#: 87020, Thermo Fisher Scientific) based on the manufacturer's protocol.…”

“…The staining protocol has been described in our previous study (51). Lung sections (5 µm) were deparaffinized and rehydrated, and then unmasked the antigens with antigen retrieval solution (10x) (Cat#: S1699, Dako, Denmark).…”

Current Perspectives on Characteristics, Compositions, and Toxicological Effects of E-Cigarettes Containing Tobacco and Menthol/Mint Flavors

“…leading to transformational changes of normal cells by e-cig derived mint/menthol flavor toxicants. Additional studies into the effects of e-cigarette exposure with developing mice found that prenatal exposure may increase chances of those mice later developing pulmonary diseases (Wang et al, 2020). A study into the effects of exposure to both e-cigarette vapor and traditional cigarette smoke showed that mice exposed to both showed altered lung function, differing from even the effects of cigarette smoke alone (Lechasseur et al, 2020).…”