Phenotype in Murine Offspring is Altered by Maternal Smoke Exposure

Background In utero exposure to cigarette smoke is a major risk factor for impaired lung function development and asthma risk in the offspring. To understand the mechanisms underlying this phenomenon animal models are required. Therefore, we aimed to establish a murine model of prenatal cigarette smoke exposure that replicates human findings. Methods Female mice were exposed daily to mainstream cigarette smoke during pregnancy starting from embryonic day (E) 2.5 until E17.5. Offspring were delivered by caesarean section at E18.5 or spontaneously. Lung and body weights were documented at birth and body weights were further monitored until postnatal day (PND) 20. Inspiratory capacity (Ic) and airway hyperresponsiveness (AHR) were measured at PND21 and 56. Histology (MLI, alveolar area), protein and mRNA quantification (Sec14L3) were done for all time points. Results Maternal weight gain during pregnancy was not affected by smoke after normalization for litter weight (E18.5). In the offspring, smoke exposure was associated with significantly impaired body and lung weight development. In smoke exposed males lung function tests revealed significantly decreased Ic at PND21 (p Conclusions Our model of prenatal smoke exposure is in agreement with findings in humans where maternal smoking during pregnancy is associated intrauterine and postnatal growth retardation and impaired lung function. Therefore, our smoke model is currently used to study gene regulatory networks and epigenetic mechanisms.