Year-end Sale % OFF 
Abstract
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.
Highlights
MATERIALS AND METHODSThe early life presentation of lung function impairment in asthma implicates a developmental disorder as the driver for disease
Working on the premise that such associations were mediated by persisting functional changes to the airway, we established a mouse model of maternal hypoxia-induced intrauterine growth restriction (IUGR) to show that IUGR female offspring were hyperresponsive to methacholine and male IUGR offspring hyporesponsive at 8 weeks of age (Wang et al, 2018)
Maternal hypoxia had no effect on litter size (Control, 3.47 ± 0.34 pups; IUGR, 3.23 ± 0.28 pups; p = 0.599) or gestational period (Control, 19.88 ± 0.15 days; IUGR, 19.94 ± 0.006 days; p = 0.507)
Summary
The early life presentation of lung function impairment in asthma implicates a developmental disorder as the driver for disease. Reduced airway function (Turner et al, 2004) and exaggerated airway narrowing to bronchial challenge (Palmer et al, 2001) is reported in infants who go on to develop asthma in childhood, a relationship which has been shown to extend to adulthood (Owens et al, 2017) These findings are consistent with early deficits in FEV1 in children with asthma (Bisgaard et al, 2012) with any decline in lung function in later life differing only marginally from the healthy lung (Phelan et al, 2002; Sears et al, 2003; James et al, 2005).
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
