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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

Lung volume (VL; A), number of alveoli in the lung [N(a,L); B], alveolar surface area [Sv(a); C], and alveolar volume (Va; D) for 2-week-old BALB/c, C3H/HeARC, and 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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f2: Lung volume (VL; A), number of alveoli in the lung [N(a,L); B], alveolar surface area [Sv(a); C], and alveolar volume (Va; D) for 2-week-old BALB/c, C3H/HeARC, and 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: Stereological analysis of lung structure. In C57BL/6 mice, lung volume (calculated by stereology) was significantly smaller in arsenic-exposed offspring compared with controls (p = 0.03). The number of alveoli in the lung (p = 0.01) and the surface area of the lung (p = 0.04) were also smaller in arsenic-exposed C57BL/6 mice compared with control mice of the same strain; however, there was no difference in the volume of the alveoli (p = 0.41) (Figure 2). We found no differences in any of the structural parameters measured between arsenic-exposed mice and control BALB/c mice or C3H/HeARC.


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)

Lung volume (VL; A), number of alveoli in the lung [N(a,L); B], alveolar surface area [Sv(a); C], and alveolar volume (Va; D) for 2-week-old BALB/c, C3H/HeARC, and 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

f2: Lung volume (VL; A), number of alveoli in the lung [N(a,L); B], alveolar surface area [Sv(a); C], and alveolar volume (Va; D) for 2-week-old BALB/c, C3H/HeARC, and 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: Stereological analysis of lung structure. In C57BL/6 mice, lung volume (calculated by stereology) was significantly smaller in arsenic-exposed offspring compared with controls (p = 0.03). The number of alveoli in the lung (p = 0.01) and the surface area of the lung (p = 0.04) were also smaller in arsenic-exposed C57BL/6 mice compared with control mice of the same strain; however, there was no difference in the volume of the alveoli (p = 0.41) (Figure 2). We found no differences in any of the structural parameters measured between arsenic-exposed mice and control BALB/c mice or C3H/HeARC.

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