Preterm birth impairs postnatal lung development in the neonatal rabbit model
Journal
Respiratory Research
ISSN
1465-993X
Date Issued
2020
Author(s)
Thomas Salaets
Margo Aertgeerts
André Gie
Janne Vignero
Derek de Winter
Yannick Regin
Greetje Vande Velde
Karel Allegaert
Jan Deprest
Jaan Toelen
Type
Resource Types::text::journal::journal article
URL Institutional Repository
Abstract
<jats:title>Abstract</jats:title><jats:sec>
<jats:title>Background</jats:title>
<jats:p>Bronchopulmonary dysplasia continues to cause important respiratory morbidity throughout life, and new therapies are needed. The common denominator of all BPD cases is preterm birth, however most preclinical research in this area focusses on the effect of hyperoxia or mechanical ventilation. In this study we investigated if and how prematurity affects lung structure and function in neonatal rabbits.</jats:p>
</jats:sec><jats:sec>
<jats:title>Methods</jats:title>
<jats:p>Pups were delivered on either day 28 or day 31. For each gestational age a group of pups was harvested immediately after birth for lung morphometry and surfactant protein B and C quantification. All other pups were hand raised and harvested on day 4 for the term pups and day 7 for the preterm pups (same corrected age) for lung morphometry, lung function testing and qPCR. A subset of pups underwent microCT and dark field imaging on day 0, 2 and 4 for terms and on day 0, 3, 5 and 7 for preterms.</jats:p>
</jats:sec><jats:sec>
<jats:title>Results</jats:title>
<jats:p>Preterm pups assessed at birth depicted a more rudimentary lung structure (larger alveoli and thicker septations) and a lower expression of surfactant proteins in comparison to term pups. MicroCT and dark field imaging revealed delayed lung aeration in preterm pups, in comparison to term pups. Preterm birth led to smaller pups, with smaller lungs with a lower alveolar surface area on day 7/day 4. Furthermore, preterm birth affected lung function with increased tissue damping, tissue elastance and resistance and decreased dynamic compliance. Expression of vascular endothelial growth factor (VEGFA) was significantly decreased in preterm pups, however in the absence of structural vascular differences.</jats:p>
</jats:sec><jats:sec>
<jats:title>Conclusions</jats:title>
<jats:p>Preterm birth affects lung structure and function at birth, but also has persistent effects on the developing lung. This supports the use of a preterm animal model, such as the preterm rabbit, for preclinical research on BPD. Future research that focuses on the identification of pathways that are involved in in-utero lung development and disrupted by pre-term birth, could lead to novel therapeutic strategies for BPD.</jats:p>
</jats:sec>
<jats:title>Background</jats:title>
<jats:p>Bronchopulmonary dysplasia continues to cause important respiratory morbidity throughout life, and new therapies are needed. The common denominator of all BPD cases is preterm birth, however most preclinical research in this area focusses on the effect of hyperoxia or mechanical ventilation. In this study we investigated if and how prematurity affects lung structure and function in neonatal rabbits.</jats:p>
</jats:sec><jats:sec>
<jats:title>Methods</jats:title>
<jats:p>Pups were delivered on either day 28 or day 31. For each gestational age a group of pups was harvested immediately after birth for lung morphometry and surfactant protein B and C quantification. All other pups were hand raised and harvested on day 4 for the term pups and day 7 for the preterm pups (same corrected age) for lung morphometry, lung function testing and qPCR. A subset of pups underwent microCT and dark field imaging on day 0, 2 and 4 for terms and on day 0, 3, 5 and 7 for preterms.</jats:p>
</jats:sec><jats:sec>
<jats:title>Results</jats:title>
<jats:p>Preterm pups assessed at birth depicted a more rudimentary lung structure (larger alveoli and thicker septations) and a lower expression of surfactant proteins in comparison to term pups. MicroCT and dark field imaging revealed delayed lung aeration in preterm pups, in comparison to term pups. Preterm birth led to smaller pups, with smaller lungs with a lower alveolar surface area on day 7/day 4. Furthermore, preterm birth affected lung function with increased tissue damping, tissue elastance and resistance and decreased dynamic compliance. Expression of vascular endothelial growth factor (VEGFA) was significantly decreased in preterm pups, however in the absence of structural vascular differences.</jats:p>
</jats:sec><jats:sec>
<jats:title>Conclusions</jats:title>
<jats:p>Preterm birth affects lung structure and function at birth, but also has persistent effects on the developing lung. This supports the use of a preterm animal model, such as the preterm rabbit, for preclinical research on BPD. Future research that focuses on the identification of pathways that are involved in in-utero lung development and disrupted by pre-term birth, could lead to novel therapeutic strategies for BPD.</jats:p>
</jats:sec>
Subjects
bronchopulmonary dysplasia
;
lung development
;
prematurity
;
preterm birth
;
animals
;
animals, newborn
;
female
;
lung
;
male
;
models, animal
;
pregnancy
;
premature birth
;
pulmonary surfactant-associated proteins
;
rabbits
;
respiratory function tests
;
tidal volume
;
surfactant protein b
;
surfactant protein c
;
vasculotropin
;
surfactant associated protein
;
animal tissue
;
article
;
controlled study
;
dendermonde rabbit
;
female
;
gestational age
;
lung alveolus
;
lung development
;
lung function
;
lung structure
;
lung volume
;
male
;
micro-computed tomography
;
new zealand white (rabbit)
;
newborn
;
nonhuman
;
polymerase chain reaction
;
postnatal development
;
premature labor
;
protein expression
;
rabbit breed
;
respiratory airflow
;
surface area
;
animal
;
animal model
;
growth, development and aging
;
leporidae
;
lung
;
lung function test
;
metabolism
;
pathology
;
physiology
;
pregnancy
;
prematurity
;
procedures
;
tidal volume