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Intrauterine growth restriction predisposes to airway inflammation without disruption of epithelial integrity in postnatal male mice

Published online by Cambridge University Press:  17 August 2020

Kevin Looi Open the ORCID record for Kevin Looi [Opens in a new window] ,
Anthony Kicic Open the ORCID record for Anthony Kicic [Opens in a new window] ,
Peter B. Noble Open the ORCID record for Peter B. Noble [Opens in a new window]  and
Kimberley C. W. Wang Open the ORCID record for Kimberley C. W. Wang [Opens in a new window]
Kevin Looi
Affiliation:
Telethon Kids Institute, The University of Western Australia, Crawley, WA6009, Australia School of Public Health, Curtin University, Bentley, WA6102, Australia
Anthony Kicic
Affiliation:
Telethon Kids Institute, The University of Western Australia, Crawley, WA6009, Australia School of Public Health, Curtin University, Bentley, WA6102, Australia Faculty of Health and Medical Science, The University of Western Australia, Crawley, WA6009, Australia Department of Respiratory and Sleep Medicine, Perth Children’s Hospital, Nedlands, WA6009, Australia Centre for Cell Therapy and Regenerative Medicine, The University of Western Australia, Crawley, WA6009, Australia
Peter B. Noble
Affiliation:
School of Human Sciences, The University of Western Australia, Crawley, WA6009, Australia
Kimberley C. W. Wang*
Affiliation:
Telethon Kids Institute, The University of Western Australia, Crawley, WA6009, Australia School of Human Sciences, The University of Western Australia, Crawley, WA6009, Australia
*
Address for correspondence: Dr Kimberley Wang, School of Human Sciences, The University of Western Australia, 35 Stirling Highway, Crawley, WA6009, Australia. Email: [email protected]
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Abstract

Evidence from animal models demonstrate that intrauterine growth restriction (IUGR) alters airway structure and function which may affect susceptibility to disease. Airway inflammation and dysregulated epithelial barrier properties are features of asthma which have not been examined in the context of IUGR. This study used a maternal hypoxia-induced IUGR mouse model to assess lung-specific and systemic inflammation and airway epithelial tight junctions (TJs) protein expression. Pregnant BALB/c mice were housed under hypoxic conditions (10.5% O2) from gestational day (GD) 11 to 17.5 (IUGR group; term, GD 21). Following hypoxic exposure, mice were returned to a normoxic environment (21% O2). A Control group was housed under normoxic conditions throughout pregnancy. Offspring weights were recorded at 2 and 8 weeks of age and euthanized for bronchoalveolar lavage (BAL) and peritoneal cavity fluid collection for inflammatory cells counts. From a separate group of mice, right lungs were collected for Western blotting of TJs proteins. IUGR offspring had greater inflammatory cells in the BAL fluid but not in peritoneal fluid compared with Controls. At 8 weeks of age, interleukin (IL)-2, IL-13, and eotaxin concentrations were higher in male IUGR compared with male Control offspring but not in females. IUGR had no effect on TJs protein expression. Maternal hypoxia-induced IUGR increases inflammatory cells in the BAL fluid of IUGR offspring with no difference in TJs protein expression. Increased cytokine release, specific to the lungs of IUGR male offspring, indicates that both IUGR and sex can influence susceptibility to airway disease.

Keywords

IUGRairway inflammationairway epitheliumtight junctions
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 12 , Issue 3 , June 2021 , pp. 496 - 504
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Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2020

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