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

Ramsey KA, Bosco A, McKenna KL, Carter KW, Elliot JG, Berry LJ, Sly PD, Larcombe AN, Zosky GR - Environ. Health Perspect. (2012)

Bottom Line: 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.Arsenic-exposed C57BL/6 mice were smaller in size, had smaller lungs, and had impaired lung mechanics compared with controls.

View Article: PubMed Central - PubMed

Affiliation: Division of Clinical Sciences, Telethon Institute for Child Health Research, Perth, Western Australia, Australia. kramsey@ichr.uwa.edu.au

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.

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Related in: MedlinePlus

Quantitation of mucus-producing cells (A) and CLCA3-(B), MUC5B- (C), and REG3γ- (D)positive epithelial cells in the airways of C57BL/6 mice. Values are expressed as the percentage of mucus-producing epithelial cells and protein-positive epithelial cells ÷ total number of epithelial cells in large, medium, and small airways of C57BL/6 mice exposed to 100 µg/L arsenic via drinking water or control water from GD8 to birth. *p < 0.05 compared with control.
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f5: Quantitation of mucus-producing cells (A) and CLCA3-(B), MUC5B- (C), and REG3γ- (D)positive epithelial cells in the airways of C57BL/6 mice. Values are expressed as the percentage of mucus-producing epithelial cells and protein-positive epithelial cells ÷ total number of epithelial cells in large, medium, and small airways of C57BL/6 mice exposed to 100 µg/L arsenic via drinking water or control water from GD8 to birth. *p < 0.05 compared with control.

Mentions: Quantification of mucus and protein in the airways. We used Alcian blue–periodic acid–Schiff staining and immunohistochemistry to quantify mucus-producing cells and CLCA3, MUC5B, and REG3γ protein in the airways of BALB/c, C3H/HeARC, and C57BL/6 mice (Figure 4). We found that arsenic exposure in utero caused mucous cell metaplasia in the large (p < 0.001) and medium (p = 0.02) airways of C57BL/6 mice and increased the expression of CLCA3 (p < 0.01) and REG3γ (p = 0.02) proteins in the large airways of C57BL/6 mice (Figure 5). The levels of MUC5B protein were low and not differentially expressed between the airways of arsenic-exposed mice and control C57BL/6 mice. There were no differences in the number of mucus-producing cells or CLCA3, MUC5B, or REG3γ proteins between the airways of arsenic and control mice of either the BALB/c or C3H/HeARC strains (data not shown).


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

Ramsey KA, Bosco A, McKenna KL, Carter KW, Elliot JG, Berry LJ, Sly PD, Larcombe AN, Zosky GR - Environ. Health Perspect. (2012)

Quantitation of mucus-producing cells (A) and CLCA3-(B), MUC5B- (C), and REG3γ- (D)positive epithelial cells in the airways of C57BL/6 mice. Values are expressed as the percentage of mucus-producing epithelial cells and protein-positive epithelial cells ÷ total number of epithelial cells in large, medium, and small airways of C57BL/6 mice exposed to 100 µg/L arsenic via drinking water or control water from GD8 to birth. *p < 0.05 compared with control.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3569690&req=5

f5: Quantitation of mucus-producing cells (A) and CLCA3-(B), MUC5B- (C), and REG3γ- (D)positive epithelial cells in the airways of C57BL/6 mice. Values are expressed as the percentage of mucus-producing epithelial cells and protein-positive epithelial cells ÷ total number of epithelial cells in large, medium, and small airways of C57BL/6 mice exposed to 100 µg/L arsenic via drinking water or control water from GD8 to birth. *p < 0.05 compared with control.
Mentions: Quantification of mucus and protein in the airways. We used Alcian blue–periodic acid–Schiff staining and immunohistochemistry to quantify mucus-producing cells and CLCA3, MUC5B, and REG3γ protein in the airways of BALB/c, C3H/HeARC, and C57BL/6 mice (Figure 4). We found that arsenic exposure in utero caused mucous cell metaplasia in the large (p < 0.001) and medium (p = 0.02) airways of C57BL/6 mice and increased the expression of CLCA3 (p < 0.01) and REG3γ (p = 0.02) proteins in the large airways of C57BL/6 mice (Figure 5). The levels of MUC5B protein were low and not differentially expressed between the airways of arsenic-exposed mice and control C57BL/6 mice. There were no differences in the number of mucus-producing cells or CLCA3, MUC5B, or REG3γ proteins between the airways of arsenic and control mice of either the BALB/c or C3H/HeARC strains (data not shown).

Bottom Line: 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.Arsenic-exposed C57BL/6 mice were smaller in size, had smaller lungs, and had impaired lung mechanics compared with controls.

View Article: PubMed Central - PubMed

Affiliation: Division of Clinical Sciences, Telethon Institute for Child Health Research, Perth, Western Australia, Australia. kramsey@ichr.uwa.edu.au

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.

Show MeSH
Related in: MedlinePlus