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In utero exposure to arsenic alters lung development and genes related to immune and mucociliary function in mice
Citation
Ramsey, KA and Bosco, A and McKenna, KL and Carter, KW and Elliot, JG and Berry, LJ and Sly, PD and Larcombe, AN and Zosky, GR, In utero exposure to arsenic alters lung development and genes related to immune and mucociliary function in mice, Environmental Health Perspectives, 121, (2) pp. 244-50. ISSN 0091-6765 (2013) [Refereed Article]
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 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.
Item Details
| Item Type: | Refereed Article |
|---|---|
| Research Division: | Biomedical and Clinical Sciences |
| Research Group: | Cardiovascular medicine and haematology |
| Research Field: | Respiratory diseases |
| Objective Division: | Health |
| Objective Group: | Public health (excl. specific population health) |
| Objective Field: | Public health (excl. specific population health) not elsewhere classified |
| UTAS Author: | Zosky, GR (Professor Graeme Zosky) |
| ID Code: | 89455 |
| Year Published: | 2013 |
| Web of Science® Times Cited: | 33 |
| Deposited By: | Medicine |
| Deposited On: | 2014-03-05 |
| Last Modified: | 2014-06-10 |
| Downloads: | 0 |
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