In Utero Exposure to Arsenic Via Drinking Water Alters Post−Natal Lung Function

Background: Epidemiological evidence has shown a link between in utero exposure to arsenic and the development of obstructive lung disease in later life. One mechanism by which this may occur is through an alteration in lung growth. Using a mouse model we aimed to determine if in utero arsenic exposure alters post−natal lung development.

Methods: Pregnant BALB/c, C3H or C57BL/6 mice were given drinking water comprised of ddH20 or ddH2O containing 100ppb As in the form of NaAsO2 from day 8 gestation to birth. Body weight and size were monitored in offspring from birth to 2 weeks of age. At 2 weeks of age mice were anaesthetised, tracheostomised and mechanically ventilated. Baseline lung volume, lung mechanics (airway resistance − Raw, tissue damping − G, tissue elastance H) and the volume dependence of lung mechanics were measured using plethysmography and the forced oscillation technique. Results: There was no difference in lung function between BALB/c mice exposed to As or control water. However, C3H mice showed increased lung volume (0.02[0.005] mL, p = 0.01) for a given body size and increased Raw (217.8[58.4] hPa.s.L−1, p = 0.001) for a given lung volume following in utero exposure to As compared to controls. Similarly, as exposed C57BL/6 mice had increased G (4038[1340] hPa.L−1, p = 0.003) and H (19008[5809] hPa.L−1, p = 0.002) for a given lung volume compared to controls.

Conclusions: These results demonstrated a clear effect of in utero arsenic exposure on post−natal lung development as measured by lung function. The strain dependence of this response provides an excellent opportunity to understand the mechanism by which this occurs and will assist in indentifying the potential link between early life arsenic exposure and the development of obstructive lung disease in later life.