Sex-Specific Alterations of the Lung Transcriptome at Birth in Mouse Offspring Prenatally Exposed to Vanilla-Flavored E-Cigarette Aerosols and Enhanced Susceptibility to Asthma

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.

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. Conclusions: 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.