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

Ramsey, Kathryn A., Bosco, Anthony, McKenna, Katherine L., Carter, Kim W., Elliot, John G., Berry, Luke J., Sly, Peter D., Larcombe, Alexander N. and Zosky, Graeme R. (2013) In utero exposure to arsenic alters lung development and genes related to immune and mucociliary function in mice. Environmental Health Perspectives, 121 2: 244-250. doi:10.1289/ehp.1205590


Author Ramsey, Kathryn A.
Bosco, Anthony
McKenna, Katherine L.
Carter, Kim W.
Elliot, John G.
Berry, Luke J.
Sly, Peter D.
Larcombe, Alexander N.
Zosky, Graeme R.
Title In utero exposure to arsenic alters lung development and genes related to immune and mucociliary function in mice
Formatted title
In utero exposure to arsenic alters lung development and genes related to immune and mucociliary function in mice
Journal name Environmental Health Perspectives   Check publisher's open access policy
ISSN 0091-6765
1552-9924
Publication date 2013-02
Sub-type Article (original research)
DOI 10.1289/ehp.1205590
Open Access Status DOI
Volume 121
Issue 2
Start page 244
End page 250
Total pages 7
Place of publication Research Triangle Park, NC, United States
Publisher U.S. Department of Health and Human Services * National Institute of Environmental Health Sciences
Collection year 2014
Language eng
Formatted 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 100 μg/L arsenic via drinking water from gestation day 8 until the birth of their ofspring. 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: Te 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, Tf2, 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.
Keyword Gene expression
Growth and development
Innate immunity
Mucociliary clearance
Toxicity
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
Queensland Children's Medical Research Institute Publications
 
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