Abstract
Background
Maternal smoking during pregnancy is a main risk factor for the offspring to develop (1) a small for gestational age phenotype at birth and (2) a chronic lung disease (e.g. asthma) later in life. However, the underlying mechanisms linking these two observations are currently not well understood. We therefore asked whether maternal smoking affects developmentally important signaling networks in lungs of offspring in late foetal stage.
Methods
Pregnant BALB/c mice were exposed to filtered air (FA) or mainstream cigarette smoke (MCS) daily from E2.5 to E17.5. Foetal lungs were collected on E18.5. Maternal blood carboxyhaemoglobin (Hb-CO) and urine cotinine was determined to assess MCS exposure. Gene expression profiling of foetal lung mRNAs and microRNAs (n=6/group and sex) was performed on Affymetrix GeneChips®. Network analysis was done using Ingenuity® software. Expression of MCS-deregulated molecules was validated by qPCR with an additional sample set.
Results
Blood Hb-CO and urine cotinine levels of MCS mice were comparable to human smokers. Lung and body weights were significantly reduced in MCS vs. FA pups at E18.5. Upstream regulator analysis of foetal pulmonary gene expression indicates MCS-induced deregulation of transcription factors (e.g. E2F7, CEBPA, SREBF1), microRNAs (e.g. miR-29b-3p, miR-30c-5p), and several downstream genes involved in a signaling network important for function and development of the respiratory system (e.g. Igf1).
Conclusions
In utero MCS exposure affects fetal pulmonary signaling networks on multiple levels including changes in transcription factor and microRNA expression. These changes might affect lung development and later disease susceptibility.
- © 2014 ERS