title: Sex-specific perinatal nicotine-induced asthma in rat offspring.
abstract: Recently, we have suggested that down-regulation of homeostatic mesenchymal peroxisome proliferator-activated receptor γ signaling after in utero nicotine exposure might contribute to asthma. Here, we have exploited an in vivo rat model of asthma to determine if the effects of perinatal nicotine exposure on offspring pulmonary function and mesenchymal markers of airway contractility in both tracheal and lung parenchymal tissue are sex specific, and whether the protection afforded by the peroxisome proliferator-activated receptor γ agonist, rosiglitazone (RGZ), against the perinatal nicotine-induced effect on offspring lung is also sex specific. Pregnant rat dams received placebo, nicotine, or nicotine plus RGZ daily from Embryonic Day 6 until Postnatal Day 21, at which time lung resistance, compliance, tracheal contractility, and the expression of structural and functional mesenchymal markers of pulmonary contractility were determined. Compared with control animals, perinatal nicotine exposure caused a significant increase in airway resistance and a decrease in airway compliance after a methacholine challenge in both male and female offspring, with more pronounced changes in the males. In contrast to this, the effects of perinatal nicotine exposure on acetylcholine-induced tracheal constriction, along with the expression of its mesenchymal markers, were observed exclusively in the male offspring. Concomitant treatment with RGZ normalized the nicotine-induced alterations in pulmonary function in both sexes, as well as the male-specific effects on acetylcholine-induced tracheal constriction, along with the affected mesenchymal markers. These data suggest that perinatal nicotine exposure causes sex-specific perinatal cigarette smoke exposure-induced asthma, providing a powerful phenotypic model for unequivocally determining the underlying nature of the cell molecular mechanism for this disease.
authors.affiliation: Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90502-2006, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Erum
authors.initials: E
authors.lastname: Naeem
authors.forename: Jia
authors.initials: J
authors.lastname: Tian
authors.forename: Vincent
authors.initials: V
authors.lastname: Lombardi
authors.forename: Kenny
authors.initials: K
authors.lastname: Kwong
authors.forename: Omid
authors.initials: O
authors.lastname: Akbari
authors.forename: John S
authors.initials: JS
authors.lastname: Torday
authors.forename: Virender K
authors.initials: VK
authors.lastname: Rehan
mesh_terms: D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn; D001249:Asthma / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D008170:Lung Compliance / Q000187:drug effects; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000473:pathology; D009538:Nicotine / Q000008:administration & dosage / Q000633:toxicity*; D047495:PPAR gamma / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077154:Rosiglitazone; D012727:Sex Characteristics; D012907:Smoking / Q000009:adverse effects; D045162:Thiazolidinediones / Q000008:administration & dosage; D014132:Trachea / Q000187:drug effects / Q000473:pathology
chemical_list: D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D009538:Nicotine