Epidemiological studies demonstrate an association between intrauterine growth restriction (IUGR) and asthma; however the underlying mechanism is unknown. We investigated the impact of maternal hypoxia-induced IUGR on airway responsiveness in male and female mice during juvenility and adulthood. Pregnant BALB/c mice were housed under hypoxic conditions for gestational days 11–17.5 and then returned to normoxic conditions for the remainder of pregnancy. A control group was housed under normoxic conditions throughout pregnancy. Offspring were studied at 2 weeks (juveniles) and 8 weeks (adults), where lung volume was assessed by plethysmography, airway responsiveness to methacholine determined by the forced oscillation technique and lungs fixed for morphometry. IUGR offspring were lighter at birth, exhibited “catch-up growth” by 2 weeks, but were again lighter in adulthood. IUGR males were “hyper-responsive” at 2 weeks and “hypo-responsive” as adults, in contrast with IUGR females who were hyper-responsive in adulthood. IUGR males had increased inner and total wall thickness at 2 weeks which resolved by adulthood, while airways in IUGR females were structurally normal throughout life. There were no differences in lung volume between Control and IUGR offspring at any age. Our data demonstrate changes in airway responsiveness as a result of IUGR that could influence susceptibility to asthma development and contribute to sexual dimorphism in asthma prevalence which switches from a male dominated disease in early life to a female dominated disease in adulthood.
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Research Article|
January 25 2018
Foetal growth restriction in mice modifies postnatal airway responsiveness in an age and sex-dependent manner
Kimberley C.W. Wang
;
1
Telethon Kids Institute, The University of Western Australia, Subiaco, Western Australia, Australia2
School of Human Sciences, The University of Western Australia, Crawley, Western Australia, Australia
Correspondence: Kimberley C. W. Wang (kimberley.wang@uwa.edu.au)
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Alexander N. Larcombe
;
Alexander N. Larcombe
1
Telethon Kids Institute, The University of Western Australia, Subiaco, Western Australia, Australia3
School of Public Health, Curtin University, Perth, Western Australia, Australia
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Luke J. Berry
;
Luke J. Berry
1
Telethon Kids Institute, The University of Western Australia, Subiaco, Western Australia, Australia
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Jude S. Morton
;
Jude S. Morton
4
Women and Children’s Health Research Institute and the Cardiovascular Research Centre, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada
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Sandra T. Davidge
;
Sandra T. Davidge
4
Women and Children’s Health Research Institute and the Cardiovascular Research Centre, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada
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Alan L. James
;
Alan L. James
5
Department of Pulmonary Physiology and Sleep Medicine, West Australian Sleep Disorders Research Institute, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia and School of Medicine and Pharmacology, The University of Western Australia, Crawley, Western Australia, Australia
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Peter B. Noble
Peter B. Noble
1
Telethon Kids Institute, The University of Western Australia, Subiaco, Western Australia, Australia2
School of Human Sciences, The University of Western Australia, Crawley, Western Australia, Australia6
Centre for Neonatal Research and Education, School of Paediatrics and Child Health, The University of Western Australia, Perth, Western Australia, Australia
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Clin Sci (Lond) (2018) 132 (2): 273-284.
Article history
Received:
November 21 2017
Revision Received:
December 15 2017
Accepted:
December 18 2017
Accepted Manuscript online:
December 20 2017
Citation
Kimberley C.W. Wang, Alexander N. Larcombe, Luke J. Berry, Jude S. Morton, Sandra T. Davidge, Alan L. James, Peter B. Noble; Foetal growth restriction in mice modifies postnatal airway responsiveness in an age and sex-dependent manner. Clin Sci (Lond) 31 January 2018; 132 (2): 273–284. doi: https://doi.org/10.1042/CS20171554
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