In Utero Exposure to Arsenic Alters Lung Development and Genes Related to Immune and Mucociliary Function in Mice

In Utero Exposure to Arsenic Alters Lung Development and Genes Related to Immune and Mucociliary Function in Mice
http://ehp.niehs.nih.gov/2012/12/1205590/

Ramsey KA, Bosco A, McKenna KL, Carter KW, Elliot JG, Berry LJ, Sly PD, Larcombe AN, Zosky GR. In Utero Exposure to Arsenic Alters Lung Development and Genes Related to Immune and Mucociliary Function in Mice. Environ Health Perspect (): .doi:10.1289/ehp.1205590

Abstract

Background:  Exposure to arsenic via drinking water is a global environmental health problem. In utero exposure to arsenic via drinking water increases the risk of lower respiratory tract infections during infancy and mortality from bronchiectasis in early adulthood.

Objectives:  We aimed to investigate how arsenic exposure in early life alters lung development and pathways involved in innate immunity.

Methods:  Pregnant BALB/c, C57BL/6 and C3H/HeARC mice were exposed to 0 (control) or 100μg/L arsenic via drinking water from day 8 of gestation until the birth of their offspring. At two weeks post-natal age mice had somatic growth, lung volume and lung mechanics measured. Fixed lungs were utilised for structural analysis. Lung tissue was collected for gene expression analysis by microarray.

Results:  The response to arsenic was genetically determined and C57BL/6 mice were the most susceptible strain. Arsenic exposed C57BL/6 mice were smaller in size, had smaller lungs and impaired lung mechanics compared with controls. Exposure to arsenic in utero up-regulated the expression of genes in the lung involved in mucous production (Clca3, Muc5b, Scgb3a1), innate immunity (Reg3γ, Tff2, Dynlrb2, Lplunc1) and lung morphogenesis (Sox2). Arsenic exposure also induced mucous cell metaplasia and increased expression of CLCA3 protein in the large airways.

Conclusions:  Alterations in somatic growth, lung development and the expression of genes involved in mucociliary clearance and innate immunity in the lung are potential mechanisms through which early life arsenic exposure impacts respiratory health.