title: Maternal smoking during pregnancy induces airway remodelling in mice offspring.
abstract: Children from smoking mothers have an increased risk of developing asthma for reasons largely unknown. The effects of maternal smoking during pregnancy on remodelling, allergic airway inflammation and hyperresponsiveness in offspring were investigated in an experimental asthma model. Mice were exposed to fresh air or cigarette smoke from 3 weeks prior to conception until birth. Offspring were exposed to house dust mite (HDM) or PBS intranasally four times per week from week 5 to week 10 after birth onwards. Maternal smoking increased airway smooth muscle layer, collagen III deposition and HDM-induced goblet cell numbers in offspring. It additionally increased methacholine responsiveness, which correlated significantly with increased airway smooth muscle layer and collagen deposition. Maternal smoking increased HDM-induced numbers of neutrophils and mast cells in lung tissue. No further effects were observed. Smoking during pregnancy induces airway remodelling in mice offspring, which may contribute to increased methacholine responsiveness. This takes place irrespective of allergen exposure but may worsen the outcome of the allergic stimulus, resulting in higher methacholine responsiveness in house dust mite-exposed offspring from smoking mothers when compared to nonsmoking mothers. The results provide a possible mechanism behind the association between maternal smoking and asthma.
authors.affiliation: Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: M J
authors.initials: MJ
authors.lastname: Blacquière
authors.forename: W
authors.initials: W
authors.lastname: Timens
authors.forename: B N
authors.initials: BN
authors.lastname: Melgert
authors.forename: M
authors.initials: M
authors.lastname: Geerlings
authors.forename: D S
authors.initials: DS
authors.lastname: Postma
authors.forename: M N
authors.initials: MN
authors.lastname: Hylkema
mesh_terms: D000485:Allergens / Q000008:administration & dosage; D000818:Animals; D000831:Animals, Newborn; D016085:Bronchoconstrictor Agents; D016207:Cytokines / Q000378:metabolism; D040001:Dermatophagoides farinae / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D020397:Goblet Cells / Q000378:metabolism; D007150:Immunohistochemistry; D016014:Linear Models; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008431:Maternal-Fetal Exchange; D016210:Methacholine Chloride; D051379:Mice; D008807:Mice, Inbred BALB C; D009130:Muscle, Smooth / Q000378:metabolism / Q000473:pathology*; D011247:Pregnancy; D012906:Smoke / Q000009:adverse effects*; D014026:Nicotiana
chemical_list: D000485:Allergens; D016085:Bronchoconstrictor Agents; D016207:Cytokines; D012906:Smoke; D016210:Methacholine Chloride