PMID- 31507442
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1664-042X (Print)
IS  - 1664-042X (Electronic)
IS  - 1664-042X (Linking)
VI  - 10
DP  - 2019
TI  - Mechanical Abnormalities of the Airway Wall in Adult Mice After Intrauterine 
      Growth Restriction.
PG  - 1073
LID - 10.3389/fphys.2019.01073 [doi]
LID - 1073
AB  - 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% O(2)) from 
      gestational day (GD) 11 to GD 17.5 (IUGR; term, GD 21). Following hypoxic 
      exposure, mice were returned to a normoxic environment (21% O(2)). 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 cmH(2)O 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.
FAU - Noble, Peter B
AU  - Noble PB
AD  - School of Human Sciences, University of Western Australia, Perth, WA, Australia.
FAU - Kowlessur, Darshinee
AU  - Kowlessur D
AD  - School of Human Sciences, University of Western Australia, Perth, WA, Australia.
AD  - Telethon Kids Institute, University of Western Australia, Perth, WA, Australia.
FAU - Larcombe, Alexander N
AU  - Larcombe AN
AD  - Telethon Kids Institute, University of Western Australia, Perth, WA, Australia.
AD  - School of Public Health, Curtin University, Perth, WA, Australia.
FAU - Donovan, Graham M
AU  - Donovan GM
AD  - Department of Mathematics, University of Auckland, Auckland, New Zealand.
FAU - Wang, Kimberley C W
AU  - Wang KCW
AD  - School of Human Sciences, University of Western Australia, Perth, WA, Australia.
AD  - Telethon Kids Institute, University of Western Australia, Perth, WA, Australia.
LA  - eng
PT  - Journal Article
DEP - 20190823
PL  - Switzerland
TA  - Front Physiol
JT  - Frontiers in physiology
JID - 101549006
PMC - PMC6716216
OTO - NOTNLM
OT  - animal models
OT  - asthma
OT  - intrauterine growth restriction
OT  - low birth weight
OT  - respiratory structure and function
EDAT- 2019/09/12 06:00
MHDA- 2019/09/12 06:01
PMCR- 2019/08/23
CRDT- 2019/09/12 06:00
PHST- 2019/06/10 00:00 [received]
PHST- 2019/08/05 00:00 [accepted]
PHST- 2019/09/12 06:00 [entrez]
PHST- 2019/09/12 06:00 [pubmed]
PHST- 2019/09/12 06:01 [medline]
PHST- 2019/08/23 00:00 [pmc-release]
AID - 10.3389/fphys.2019.01073 [doi]
PST - epublish
SO  - Front Physiol. 2019 Aug 23;10:1073. doi: 10.3389/fphys.2019.01073. eCollection 
      2019.