In utero exposure to low dose arsenic via drinking water impairs early life lung mechanics in mice

Abstract

Background: Exposure to arsenic via drinking water is a significant environmental issue affecting millions of people around the world. Exposure to arsenic during foetal development has been shown to impair somatic growth and increase the risk of developing chronic respiratory diseases. The aim of this study was to determine if in utero exposure to low dose arsenic via drinking water is capable of altering lung growth and postnatal lung mechanics.

Methods: Pregnant C57BL/6 mice were given drinking water containing 0, 10 (current World Health Organisation (WHO) maximum contaminant level) or 100 μg/L arsenic from gestational day 8 to birth. Birth outcomes and somatic growth were monitored. Plethysmography and the forced oscillation technique were used to collect measurements of lung volume, lung mechanics, pressure-volume curves and the volume dependence of lung mechanics in male and female offspring at two, four, six and eight weeks of age.

Results: In utero exposure to low dose arsenic via drinking water resulted in low birth weight and impaired parenchymal lung mechanics during infancy. Male offspring were more susceptible to the effects of arsenic on growth and lung mechanics than females. All alterations to lung mechanics following in utero arsenic exposure were recovered by adulthood.

Conclusions: Exposure to arsenic at the current WHO maximum contaminant level in utero impaired somatic growth and the development of the lungs resulting in alterations to lung mechanics during infancy. Deficits in growth and lung development in early life may contribute to the increased susceptibility of developing chronic respiratory disease in arsenic exposed human populations.

Figure 1

Body weight and thoracic gas volume in two, four, six and eight week old male and female C57BL/6 offspring exposedin uteroto drinking water containing 0 (control), 10 or 100μg/L arsenic (mean). There were no differences in body weight or thoracic gas volume between offspring exposed to arsenic and controls at two, four, six or eight weeks of age.

Figure 2

Airway resistance, tissue damping and tissue elastance at P_rs = 0 cmH₂0 in two week old male and female C57BL/6 offspring exposed in utero to drinking water containing 0 (control), 10 or 100μg/L arsenic (mean ± SD). Tissue damping and tissue elastance were higher in two week old male offspring exposed to 10 or 100μg/L arsenic compared with controls. There was no effect of arsenic, at either dose, on lung mechanics in two week female offspring (* indicates significantly different to controls).

Figure 3

Pressure-volume curve during inflation to P_rs = 20 cmH₂O and exhalation to functional residual capacity plotted against TGV in male and female two week old C57BL/6 offspring exposed in utero to drinking water containing 0 (control) or 100μg/L arsenic (mean ± SD). The maximum TGV reached during inflation was lower in male offspring exposed to 100μg/L arsenic compared to male controls. There was no effect of 100μg/L arsenic on maximum TGV in two week female offspring (* indicates significantly different to controls).

Figure 4

Volume dependence of airway resistance, tissue damping and tissue elastance during inflation to P_rs = 20 cmH₂O and exhalation to functional residual capacity in two week old male (A, B, C) and female (D, E, F) offspring exposed in utero to drinking water containing 0 (control) or 100μg/L arsenic (mean). Tissue damping and tissue elastance at P_rs = 20 cmH₂O were significantly higher in male offspring exposed to 100μg/L arsenic compared to male controls. There was no effect of arsenic exposure on tissue mechanics in females and no effect of arsenic on airway resistance in either sex (* indicates significantly different to controls).

Figure 5

Tissue elastance at P_rs = 0 cmH₂0 in two, four, six and eight week old male and female C57BL/6 offspring exposed in utero to drinking water containing 0 (control), 10 or 100μg/L arsenic (mean). Arsenic-induced impairments to lung mechanics in male two week old offspring were resolved at four, six and eight weeks of age (* indicates significantly different to controls).