Limits...
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.

Show MeSH

Related in: MedlinePlus

Airway resistance (Raw; A–C), tissue damping (G; D–F) and tissue elastance (H; G–I) plotted against TGV for 2-week-old BALB/c (A,D,G), C3H/HeARC (B,E,H), and C57BL/6 (C,F,I) 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


getmorefigures.php?uid=PMC3569690&req=5

f1: Airway resistance (Raw; A–C), tissue damping (G; D–F) and tissue elastance (H; G–I) plotted against TGV for 2-week-old BALB/c (A,D,G), C3H/HeARC (B,E,H), and C57BL/6 (C,F,I) mice exposed to 100 µg/L arsenic via drinking water or control water from GD8 to birth. *p < 0.05 compared with control.

Mentions: TGV and lung mechanics. Arsenic-exposed C57BL/6 mice were significantly smaller in body weight (p < 0.001) than control offspring at 2 weeks of age and had significantly lower TGV than controls (p < 0.001), even after adjusting for snout-vent length (p = 0.04) [see Supplemental Material, Figure S2 (http://dx.doi.org/10.1289/ehp.1205590)]. Arsenic-exposed C57BL/6 mice had significantly higher tissue damping and tissue elastance (p < 0.001 in both cases) compared with C57BL/6 controls (Figure 1). These differences were maintained after adjusting for TGV (p = 0.006 and p = 0.004, respectively). There was no effect of arsenic on airway resistance (p = 0.29) in C57BL/6 mice, which was maintained after adjusting for TGV (p = 0.78).


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)

Airway resistance (Raw; A–C), tissue damping (G; D–F) and tissue elastance (H; G–I) plotted against TGV for 2-week-old BALB/c (A,D,G), C3H/HeARC (B,E,H), and C57BL/6 (C,F,I) 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

f1: Airway resistance (Raw; A–C), tissue damping (G; D–F) and tissue elastance (H; G–I) plotted against TGV for 2-week-old BALB/c (A,D,G), C3H/HeARC (B,E,H), and C57BL/6 (C,F,I) mice exposed to 100 µg/L arsenic via drinking water or control water from GD8 to birth. *p < 0.05 compared with control.
Mentions: TGV and lung mechanics. Arsenic-exposed C57BL/6 mice were significantly smaller in body weight (p < 0.001) than control offspring at 2 weeks of age and had significantly lower TGV than controls (p < 0.001), even after adjusting for snout-vent length (p = 0.04) [see Supplemental Material, Figure S2 (http://dx.doi.org/10.1289/ehp.1205590)]. Arsenic-exposed C57BL/6 mice had significantly higher tissue damping and tissue elastance (p < 0.001 in both cases) compared with C57BL/6 controls (Figure 1). These differences were maintained after adjusting for TGV (p = 0.006 and p = 0.004, respectively). There was no effect of arsenic on airway resistance (p = 0.29) in C57BL/6 mice, which was maintained after adjusting for TGV (p = 0.78).

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