The Effects of in Utero Exposure to Aerosols Generated by Electronic Nicotine Delivery Systems in Neonatal and Adult Offspring

Recently, electronic nicotine delivery systems (ENDS) have become increasingly popular alternatives to cigarette smoking and are perceived as “safe” substitutes. The effects that these devices have on healthy adult lungs are still not fully understood, much less the effects on vulnerable populations such as expectant mothers and neonates. In an effort to better understand the potentially detrimental outcomes that gestational usage may have on both mothers and offspring, we conducted mouse studies on in utero exposures to both, third generation (“box mod”) ENDS aerosols and fourth generation (“pod mod”) JUUL aerosols. In exposures using the box mod device, in utero e-cig exposed offspring displayed decreased birth weight, which was sustained until post-natal day (PND) 5. At the onset of alveolargenesis, the offspring also exhibited lung gene dysregulation related to Wnt signaling and epigenetic modifying enzymes (~120 and ~40 dysregulated genes in females and males, respectively). In addition, in utero e-cig exposures decreased lung collagen content at PND5 and impaired lung function at PND11. These data suggest that in utero exposures to e-cig aerosol may results in lasting lung function limitations. In the study concerning the popular ‘JUUL’ device, we found that neonates exposed to ENDS aerosol in utero exhibited decreased birth weight and length along with significantly decreased weight gain through 3 weeks of age. These physical growth restrictions were accompanied by modifications to the lung transcriptome, primarily associated with Wnt signaling, regulation of epithelial-mesenchymal transition pathway, and methylation of DNA. During adulthood, in utero JUUL-exposed offspring challenged with House Dust Mite (HDM) demonstrated exacerbated markers of airway hyperresponsiveness, altered lung macrophage number, and significant transcriptome dysregulation associated with allergies and asthma (33 and 53 dysregulated genes in males and females, respectively). Overall, these from mice data show that maternal usage of either third or fourth generation ENDS devices restrict fetal growth and weight gain. Also, while third generation devices seem to be detrimental to mouse lung development and alveolargenesis, fourth generation devices induce epigenetic changes which may exacerbate allergic asthma in adult offspring. Our studies indicate that ENDS usage during pregnancy affects the pulmonary health of the offspring