University of Tasmania

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In utero exposure to arsenic alters lung development and genes related to immune and mucociliary function in mice

journal contribution
posted on 2023-05-17, 22:53 authored by Ramsey, KA, Bosco, A, McKenna, KL, Carter, KW, Elliot, JG, Berry, LJ, Sly, PD, Larcombe, AN, Graeme ZoskyGraeme Zosky
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 100 μg/L arsenic via drinking water from gestation day 8 until the birth of their offspring. We measured somatic growth, lung volume, and lung mechanics of mice at 2 weeks of age. We used fixed lungs for structural analysis and collected lung tissue for gene expression analysis by microarray. RESULTS: The response to arsenic was genetically determined, and C57BL/6 mice were the most susceptible. Arsenic-exposed C57BL/6 mice were smaller in size, had smaller lungs, and had impaired lung mechanics compared with controls. Exposure to arsenic in utero up-regulated the expression of genes in the lung involved in mucus 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.


Publication title

Environmental Health Perspectives








Tasmanian School of Medicine


Us Dept Health Human Sciences Public Health Science

Place of publication

Natl Inst Health, Natl Inst Environmental Health Sciences, Po Box 12233, Res Triangle Pk, USA, Nc, 27709-2233

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  • Restricted

Socio-economic Objectives

Public health (excl. specific population health) not elsewhere classified

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