In utero cigarette smoke exposure results in impaired growth and impaired lung function in neonatal BALB/C mice

Background: Many epidemiological studies link in utero and/or early life tobacco smoke exposure to altered lung function, and respiratory disease in children. There is difficulty, however, in separating the effects of pre- and postnatal cigarette smoke exposure on lung function. We used a mouse model to assess the effects of in utero cigarette smoke exposure on early life lung function in the absence of potential confounders.

Methods: We exposed pregnant BALB/c mice to 6 cigarettes day-1 from day 8 to day 20 of gestation. At two weeks of age, pups were weighed and had their lung volumes and baseline lung mechanics measured via the forced oscillation technique. The volume dependence of lung mechanics was investigated by slowly inflating the lungs of the pups to 20 cm H2O.

Results: Pups born to mothers exposed to cigarette smoke (CS) were significantly lighter (6.76 ± 0.76 g vs. 7.72 ± 0.68 g) and had significantly lower lung volumes (0.123 ± 0.02 ml vs. 0.149 ± 0.02 ml) than control (air) pups. Respiratory mechanics were adversely impacted by CS exposure. CS pups had significantly higher baseline airway resistance (Raw), tissue damping (G) and tissue elastance (H), however these differences were due to their lower lung volumes. As lungs were inflated, both G and H were increased excessively in CS-exposed pups, while Raw and hysteresivity were not affected. CS pups had significantly higher G and H at Prs = 20 cm H2O when compared to Air pups. There were no effects of sex on responses.

Conclusions: We show that in utero tobacco smoke exposure significantly impacts early life growth and lung function in mice. These changes may partially explain the susceptibility of infants born to mothers who smoke to early respiratory disease and chronic respiratory disease as adults.