Deregulated pulmonary growth hormones after intrauterine smoke exposure. Mus musculus

Background: In utero smoke exposure is a recognized risk factor for impaired lung function development and a significant risk factor for airway disease. Despite intensive anti-tobacco campaigns the prevalence of smoking pregnant women has remained high requiring additional strategies to protect the offspring’s lung. To achieve this goal, it is critical to understand the mechanisms how disease risks are established in early life. Objective: To develop an animal model that recapitulates clinical findings in prenatally exposed children to allow the investigation of early molecular changes in the lung. Methods: Pregnant mice were exposed to active smoking from gestational day (GD) 2.5 until caesarean section or spontaneous delivery. After careful maternal characterization, we monitored weight development, lung function, and airway remodeling in offspring. mRNA/miRNA arrays were performed in fetal lungs (GD18.5), followed by network analyses, qPCR and histone analyses. Overall design: We performed small RNA expression microarray analysis on fetal (E18.5) lung tissue derived from mothers exposed to smoke or from untreated mothers.