Transient postnatal lung changes on alveolar development after in utero and lactation exposure to nicotine

ABSTRACT: Purpose: The goal of this study is to address the consequences of in utero and early life nicotine exposure on alveolar phase of lung development in mice Methods: A mouse model of gestational and early life nicotine exposure was used in this study. Briefly, Nicotine (200 mg/L) was supplied immediately after mating and administered to the females in drinking water supplemented with 2% saccharin for the whole period of gestation and lactation (nicotine group). As a control, we used drinking water with 2% saccharin (saccharin group). Pups born from nicotine-exposed or control mothers were collected at different postnatal days (PNDs) and their lungs were subjected to RNAseq, western blot, histological and detailed stereological analysis. Results: Among 13 827 genes tested, nicotine treatment induced an upregulation of 2098 and downregulation of 1859. Pathway analysis performed with MetaCore software (https://portal.genego.com/) (threshold of 2 and p<0.05) identified several different pathways as upregulated upon nicotine exposure, namely cell cycle, epithelial to mesenchymal transition, stem cell related pathway, WNT signaling pathway, stromal-epithelial interaction, cell adhesion and DNA damage. Furthermore, majority of downregulated genes were associated with the immune system. Conclusions: Our results indicate that in utero and early life nicotine exposure induces extensive changes in gene expression following the birth of mice that reflects in accelerated kinetics of lung development. This effect, however, is transient, and not lomger detectable by pnd16. On the other hand, nicotine decreased proliferation and endothelial cell density detected at pnd16, thereby affecting on of two main cell lines involved in oxygen exchange. This results are important in the context of growing interest for nicotine patch replacement therapy and electronic cigarettes.

ORGANISM(S): Mus musculus

PROVIDER: GSE102239 | GEO | 2020/02/11

REPOSITORIES: GEO