Mechanical Abnormalities of the Airway Wall in Adult Mice After Intrauterine Growth Restriction
© Copyright © 2019 Noble, Kowlessur, Larcombe, Donovan and Wang. Developmental abnormalities of airways may impact susceptibility to asthma in later life. We used a maternal hypoxia-induced mouse model of intrauterine growth restriction (IUGR) to examine changes in mechanical properties of the airwa...
| Main Authors: | , , , , |
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| Format: | Journal Article |
| Language: | English |
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FRONTIERS MEDIA SA
2019
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| Online Access: | http://hdl.handle.net/20.500.11937/76577 |
| _version_ | 1848763722001022976 |
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| author | Noble, P.B. Kowlessur, D. Larcombe, Alexander Donovan, G.M. Wang, K.C.W. |
| author_facet | Noble, P.B. Kowlessur, D. Larcombe, Alexander Donovan, G.M. Wang, K.C.W. |
| author_sort | Noble, P.B. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | © Copyright © 2019 Noble, Kowlessur, Larcombe, Donovan and Wang. Developmental abnormalities of airways may impact susceptibility to asthma in later life. We used a maternal hypoxia-induced mouse model of intrauterine growth restriction (IUGR) to examine changes in mechanical properties of the airway wall. Pregnant BALB/c mice were housed under hypoxic conditions (10.5% O2) from gestational day (GD) 11 to GD 17.5 (IUGR; term, GD 21). Following hypoxic exposure, mice were returned to a normoxic environment (21% O2). A control group of pregnant mice were housed under normoxic conditions throughout pregnancy. At 8 weeks postnatal age, offspring were euthanized and a tracheasectomy performed. Tracheal segments were studied in organ baths to measure active airway smooth muscle (ASM) stress to carbachol and assess passive mechanical properties (stiffness) from stress-strain curves. In a separate group of anesthetized offspring, the forced oscillation technique was used to examine airway mechanics from relative changes in airway conductance during slow inflation and deflation between 0 and 20 cmH2O transrespiratory pressure. From predicted radius-pressure loops, storage and loss moduli and hysteresivity were calculated. IUGR offspring were lighter at birth (p < 0.05) and remained lighter at 8 weeks of age (p < 0.05) compared with Controls. Maximal stress was reduced in male IUGR offspring compared with Controls (p < 0.05), but not in females. Sensitivity to contractile agonist was not affected by IUGR or sex. Compared with the Control group, airways from IUGR animals were stiffer in vitro (p < 0.05). In vivo, airway hysteresivity (p < 0.05) was increased in the IUGR group, but there was no difference in storage or loss moduli between groups. In summary, the effects of IUGR persist to the mature airway wall, where there are clear abnormalities to ASM contractile properties and passive wall mechanics. We propose that mechanical abnormalities of the airway wall acquired through disrupted fetal growth impact susceptibility to disease. |
| first_indexed | 2025-11-14T11:07:58Z |
| format | Journal Article |
| id | curtin-20.500.11937-76577 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-14T11:07:58Z |
| publishDate | 2019 |
| publisher | FRONTIERS MEDIA SA |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-765772019-10-18T07:32:16Z Mechanical Abnormalities of the Airway Wall in Adult Mice After Intrauterine Growth Restriction Noble, P.B. Kowlessur, D. Larcombe, Alexander Donovan, G.M. Wang, K.C.W. Science & Technology Life Sciences & Biomedicine Physiology intrauterine growth restriction low birth weight animal models asthma respiratory structure and function METHACHOLINE-INDUCED BRONCHOCONSTRICTION SMOOTH-MUSCLE LUNG-FUNCTION DEEP INSPIRATION PREDICTS ASTHMA BIRTH-WEIGHT RESPONSIVENESS STIFFNESS HEALTH BRONCHODILATION © Copyright © 2019 Noble, Kowlessur, Larcombe, Donovan and Wang. Developmental abnormalities of airways may impact susceptibility to asthma in later life. We used a maternal hypoxia-induced mouse model of intrauterine growth restriction (IUGR) to examine changes in mechanical properties of the airway wall. Pregnant BALB/c mice were housed under hypoxic conditions (10.5% O2) from gestational day (GD) 11 to GD 17.5 (IUGR; term, GD 21). Following hypoxic exposure, mice were returned to a normoxic environment (21% O2). A control group of pregnant mice were housed under normoxic conditions throughout pregnancy. At 8 weeks postnatal age, offspring were euthanized and a tracheasectomy performed. Tracheal segments were studied in organ baths to measure active airway smooth muscle (ASM) stress to carbachol and assess passive mechanical properties (stiffness) from stress-strain curves. In a separate group of anesthetized offspring, the forced oscillation technique was used to examine airway mechanics from relative changes in airway conductance during slow inflation and deflation between 0 and 20 cmH2O transrespiratory pressure. From predicted radius-pressure loops, storage and loss moduli and hysteresivity were calculated. IUGR offspring were lighter at birth (p < 0.05) and remained lighter at 8 weeks of age (p < 0.05) compared with Controls. Maximal stress was reduced in male IUGR offspring compared with Controls (p < 0.05), but not in females. Sensitivity to contractile agonist was not affected by IUGR or sex. Compared with the Control group, airways from IUGR animals were stiffer in vitro (p < 0.05). In vivo, airway hysteresivity (p < 0.05) was increased in the IUGR group, but there was no difference in storage or loss moduli between groups. In summary, the effects of IUGR persist to the mature airway wall, where there are clear abnormalities to ASM contractile properties and passive wall mechanics. We propose that mechanical abnormalities of the airway wall acquired through disrupted fetal growth impact susceptibility to disease. 2019 Journal Article http://hdl.handle.net/20.500.11937/76577 10.3389/fphys.2019.01073 English http://creativecommons.org/licenses/by/4.0/ FRONTIERS MEDIA SA fulltext |
| spellingShingle | Science & Technology Life Sciences & Biomedicine Physiology intrauterine growth restriction low birth weight animal models asthma respiratory structure and function METHACHOLINE-INDUCED BRONCHOCONSTRICTION SMOOTH-MUSCLE LUNG-FUNCTION DEEP INSPIRATION PREDICTS ASTHMA BIRTH-WEIGHT RESPONSIVENESS STIFFNESS HEALTH BRONCHODILATION Noble, P.B. Kowlessur, D. Larcombe, Alexander Donovan, G.M. Wang, K.C.W. Mechanical Abnormalities of the Airway Wall in Adult Mice After Intrauterine Growth Restriction |
| title | Mechanical Abnormalities of the Airway Wall in Adult Mice After Intrauterine Growth Restriction |
| title_full | Mechanical Abnormalities of the Airway Wall in Adult Mice After Intrauterine Growth Restriction |
| title_fullStr | Mechanical Abnormalities of the Airway Wall in Adult Mice After Intrauterine Growth Restriction |
| title_full_unstemmed | Mechanical Abnormalities of the Airway Wall in Adult Mice After Intrauterine Growth Restriction |
| title_short | Mechanical Abnormalities of the Airway Wall in Adult Mice After Intrauterine Growth Restriction |
| title_sort | mechanical abnormalities of the airway wall in adult mice after intrauterine growth restriction |
| topic | Science & Technology Life Sciences & Biomedicine Physiology intrauterine growth restriction low birth weight animal models asthma respiratory structure and function METHACHOLINE-INDUCED BRONCHOCONSTRICTION SMOOTH-MUSCLE LUNG-FUNCTION DEEP INSPIRATION PREDICTS ASTHMA BIRTH-WEIGHT RESPONSIVENESS STIFFNESS HEALTH BRONCHODILATION |
| url | http://hdl.handle.net/20.500.11937/76577 |