title: Development of an experimental model of maternal allergic asthma during pregnancy.
abstract: Maternal asthma during pregnancy adversely affects pregnancy outcomes but identification of the cause/s, and the ability to evaluate interventions, is limited by the lack of an appropriate animal model. We therefore aimed to characterise maternal lung and cardiovascular responses and fetal-placental growth and lung surfactant levels in a sheep model of allergic asthma. Immune and airway functions were studied in singleton-bearing ewes, either sensitised before pregnancy to house dust mite (HDM, allergic, n = 7) or non-allergic (control, n = 5), and subjected to repeated airway challenges with HDM (allergic group) or saline (control group) throughout gestation. Maternal lung, fetal and placental phenotypes were characterised at 140 ± 1 days gestational age (term, ∼147 days). The eosinophil influx into lungs was greater after HDM challenge in allergic ewes than after saline challenge in control ewes before mating and in late gestation. Airway resistance increased throughout pregnancy in allergic but not control ewes, consistent with increased airway smooth muscle in allergic ewes. Maternal allergic asthma decreased relative fetal weight (-12%) and altered placental phenotype to a more mature form. Expression of surfactant protein B mRNA was 48% lower in fetuses from allergic ewes than controls, with a similar trend for surfactant protein D. Thus, allergic asthma in pregnant sheep modifies placental phenotype, and inhibits fetal growth and lung development consistent with observations from human pregnancies. Preconceptional allergen sensitisation and repeated airway challenges in pregnant sheep therefore provides an animal model to identify mechanisms of altered fetal development and adverse pregnancy outcomes caused by maternal asthma in pregnancy.
authors.affiliation: Robinson Research Institute and School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, SA, 5005, Australia.|Mater Medical Research Institute, University of Queensland, Brisbane, Qld, 4101, Australia.
authors.forename: Vicki L
authors.initials: VL
authors.lastname: Clifton
authors.affiliation: The Ritchie Centre, Hudson Institute of Medical Research, Monash University, Clayton, VIC, 3168, Australia.|Department of Obstetrics and Gynaecology, Monash University, Clayton, VIC, 3168, Australia.
authors.forename: Timothy J M
authors.initials: TJ
authors.lastname: Moss
authors.affiliation: Robinson Research Institute and School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, SA, 5005, Australia.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Wooldridge
authors.affiliation: Robinson Research Institute and School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, SA, 5005, Australia.
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Gatford
authors.affiliation: Department of Physiology, Monash University, Clayton, VIC, 3168, Australia.
authors.forename: Bahar
authors.initials: B
authors.lastname: Liravi
authors.affiliation: Department of Physiology, Monash University, Clayton, VIC, 3168, Australia.
authors.forename: Dasom
authors.initials: D
authors.lastname: Kim
authors.affiliation: FOODplus Research Centre, School of Agriculture, Food and Wine, The University of Adelaide, Adelaide, SA, 5005, Australia.
authors.forename: Beverly S
authors.initials: BS
authors.lastname: Muhlhausler
authors.affiliation: Early Origins of Adult Health Research Group, School of Pharmacy and Medical Sciences, Sansom Institute for Health Research, University of South Australia, Adelaide, SA, 5001, Australia.
authors.forename: Janna L
authors.initials: JL
authors.lastname: Morrison
authors.affiliation: Department of Physiology, Monash University, Clayton, VIC, 3168, Australia.|School of Biomedical Sciences, Peninsula Campus, Monash University, Frankston, VIC, 3199, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Davies
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, 3168, Australia.
authors.forename: Robert
authors.initials: R
authors.lastname: De Matteo
authors.affiliation: The Ritchie Centre, Hudson Institute of Medical Research, Monash University, Clayton, VIC, 3168, Australia.|Department of Obstetrics and Gynaecology, Monash University, Clayton, VIC, 3168, Australia.
authors.forename: Megan J
authors.initials: MJ
authors.lastname: Wallace
authors.affiliation: The Ritchie Centre, Hudson Institute of Medical Research, Monash University, Clayton, VIC, 3168, Australia.|Department of Physiology, Monash University, Clayton, VIC, 3168, Australia.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Bischof
mesh_terms: D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology / Q000633:toxicity; D001249:Asthma / Q000209:etiology / Q000503:physiopathology*; D004195:Disease Models, Animal; D005260:Female; D011247:Pregnancy; D011248:Pregnancy Complications / Q000209:etiology / Q000503:physiopathology*; D012756:Sheep
chemical_list: D039741:Antigens, Dermatophagoides