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

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 Wnt signaling, which is essential to lung organogenesis. Thus, our data indicate that maternal vaping impairs pregnancy outcomes, alters fetal lung structure, and dysregulates the Wnt signaling. This study provides experimental evidence for future regulations of e-cig products for pregnant women and developmentally vulnerable populations.

Sub-ohm vaping increases the levels of carbonyls, is cytotoxic, and alters gene expression in human bronchial epithelial cells exposed at the air–liquid interface

“…1) may not be solely responsible for the cellular toxicity (Figs. 4, 5, 6, 7, 8), but that the intrinsic toxicity of the flavoring chemical, such as the well-known deleterious effects of cinnamaldehyde [36,[46][47][48][49][50], may also play a significant role. Overall, we showed (1) that sub-ohm (0.15 Ω) vaping produces more toxic chemicals than regular (1.5 Ω) vaping, and that this can be flavor specific; and (2) that sub-ohm vaping induces detrimental effects to human lung epithelial cells.…”

“…1), the enhanced toxicity of the cinnamon-flavored e-cig aerosol (Figs. 4, 7, 8) may be due to cinnamaldehyde, the primary flavoring chemical of cinnamon-based e-liquids, which was shown to be highly toxic in both in vitro and in vivo models [36,[46][47][48][49][50]64]. For instance, using a zebrafish model it was shown that the presence of cinnamaldehyde in various e-liquids, including in bubble gum flavored-e-liquids, was mainly responsible for the harmful developmental effects observed [65].…”

“…For H&E staining of the cells, the transwell inserts were first embed in agarose as per STEMCELL Technologies Product procedures, and then paraffin-embedded and sectioned (5 μm thin). H&E staining was performed using standard protocols [36]. All experiments were performed with cells from passages 2 to 6.…”

“…Aside from the carbonyls produced in the e-cig aerosol (Fig. 1), this may be due to other factors, including cinnamaldehyde, an e-cig flavoring chemical showed to be toxic in vitro and in vivo [36,[46][47][48][49][50].…”

Past as Prologue: Vaping Effects on the Developing Lung

“…It is well established that maternal exposure to systemic nicotine interferes with airway and airspace development in animal models [1,2]. Recent efforts have further characterized transplacental effects of maternal nicotine and e-cigarette vapor on fetal lung development and introduced the concept of susceptibilities to injury in various compartments that may persist into adulthood [3][4][5].…”