title: In utero exposure to arsenic alters lung development and genes related to immune and mucociliary function in mice.
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Division of Clinical Sciences, Telethon Institute for Child Health Research, Perth, Western Australia, Australia. kramsey@ichr.uwa.edu.au
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Ramsey
authors.forename: Anthony
authors.initials: A
authors.lastname: Bosco
authors.forename: Katherine L
authors.initials: KL
authors.lastname: McKenna
authors.forename: Kim W
authors.initials: KW
authors.lastname: Carter
authors.forename: John G
authors.initials: JG
authors.lastname: Elliot
authors.forename: Luke J
authors.initials: LJ
authors.lastname: Berry
authors.forename: Peter D
authors.initials: PD
authors.lastname: Sly
authors.forename: Alexander N
authors.initials: AN
authors.lastname: Larcombe
authors.forename: Graeme R
authors.initials: GR
authors.lastname: Zosky
mesh_terms: D000818:Animals; D001151:Arsenic / Q000633:toxicity*; D002923:Cilia / Q000502:physiology*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D008168:Lung / Q000187:drug effects* / Q000196:embryology / Q000276:immunology / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D016133:Polymerase Chain Reaction; D011247:Pregnancy
chemical_list: D001151:Arsenic