In utero exposure to electronic-cigarette aerosols decreases lung fibrillar collagen content, increases Newtonian resistance and induces sex-specific molecular signatures in neonatal mice

Authors

Kerin M. Cahill, Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Skip Bertman Dr., Baton Rouge, LA 70803 USA.
Manas R. Gartia, Department of Mechanical and Industrial Engineering, Louisiana State University, Baton Rouge, LA 70803 USA.
Sushant Sahu, Department of Chemistry, University of Louisiana at Lafayette, Lafayette, LA 70504 USA.
Sarah R. Bergeron, Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Skip Bertman Dr., Baton Rouge, LA 70803 USA.
Linda M. Heffernan, Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Skip Bertman Dr., Baton Rouge, LA 70803 USA.
Daniel B. Paulsen, Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803 USA.
Arthur L. Penn, Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Skip Bertman Dr., Baton Rouge, LA 70803 USA.
Alexandra Noël, Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Skip Bertman Dr., Baton Rouge, LA 70803 USA.

Document Type

Article

Publication Date

4-1-2022

Abstract

Approximately 7% of pregnant women in the United States use electronic-cigarette (e-cig) devices during pregnancy. There is, however, no scientific evidence to support e-cig use as being 'safe' during pregnancy. Little is known about the effects of fetal exposures to e-cig aerosols on lung alveologenesis. In the present study, we tested the hypothesis that in utero exposure to e-cig aerosol impairs lung alveologenesis and pulmonary function in neonates. Pregnant BALB/c mice were exposed 2 h a day for 20 consecutive days during gestation to either filtered air or cinnamon-flavored e-cig aerosol (36 mg/mL of nicotine). Lung tissue was collected in offspring during lung alveologenesis on postnatal day (PND) 5 and PND11. Lung function was measured at PND11. Exposure to e-cig aerosol in utero led to a significant decrease in body weights at birth which was sustained through PND5. At PND5, in utero e-cig exposures dysregulated genes related to signaling and epigenetic modifications in both females (~ 120 genes) and males (40 genes). These alterations were accompanied by reduced lung fibrillar collagen content at PND5-a time point when collagen content is close to its peak to support alveoli formation. In utero exposure to e-cig aerosol also increased the Newtonian resistance of offspring at PND11, suggesting a narrowing of the conducting airways. At PND11, in females, transcriptomic dysregulation associated with epigenetic alterations was sustained (17 genes), while signaling dysregulation was largely resolved (10 genes). In males, at PND11, the expression of only 4 genes associated with epigenetics was dysregulated, while 16 related-genes were altered. These data demonstrate that in utero exposures to cinnamon-flavored e-cig aerosols alter lung structure and function and induce sex-specific molecular signatures during lung alveologenesis in neonatal mice. This may reflect epigenetic programming affecting lung disease development later in life.

Publication Source (Journal or Book title)

Toxicological research

First Page

205

Last Page

224

Recommended Citation

Cahill, K. M., Gartia, M. R., Sahu, S., Bergeron, S. R., Heffernan, L. M., Paulsen, D. B., Penn, A. L., & Noël, A. (2022). In utero exposure to electronic-cigarette aerosols decreases lung fibrillar collagen content, increases Newtonian resistance and induces sex-specific molecular signatures in neonatal mice. Toxicological research, 38 (2), 205-224. https://doi.org/10.1007/s43188-021-00103-3