Pulmonary vascular endothelial growth factor expression and disaturated phospholipid content in a chicken model of hypoxia-induced fetal growth restriction.
BACKGROUND
Prenatal hypoxia is an important cause of intrauterine growth retardation that affects fetal lung maturation, although previous studies have rendered conflicting results. The fetal chicken model allows the study of the isolated effects of hypoxia during development.


OBJECTIVE
We hypothesized that prenatal hypoxia would differentially affect surfactant synthesis, depending on timing and duration of hypoxia. Pulmonary vascular endothelial growth factor (VEGF) expression was analyzed as a possible link between oxygen sensing and surfactant production.


METHODS
Fertilized White Leghorn eggs were incubated in normoxia, hyperoxia (60% O(2)) from day 15 or hypoxia (15% O(2)) from either day 6 or day 15 of incubation. Whole lung disaturated phospholipids (DSPL) and mRNA expression of VEGF isoforms were quantified at day 16 and 19.


RESULTS
Lung DSPL content increased approximately threefold between day 16 and 19 in control animals. Both hypoxia and hyperoxia from day 15 significantly increased DSPL content at day 19 versus control (103 +/- 22 and 116 +/- 18 vs. 81 +/- 15 microg/mg protein, p < 0.01 and p < 0.001, respectively), while long-term hypoxia tended to decrease DSPL content (65 +/- 17 microg/mg protein, p = 0.056). No differences in DSPL content were observed at day 16. Short-term hypoxia transiently up-regulated VEGF146 1.5-fold at day 16 (p < 0.05). A similar trend was observed for VEGF122 (p = 0.058) and VEGF190 (p = 0.08), while no differences were present at day 19.


CONCLUSIONS
Both prenatal hypoxia and hyperoxia induced during critical windows of lung development differentially modulate surfactant synthesis. Our data support the concept that fetal oxygen tension is a key signal in the regulation of the surfactant system.
Been
Jasper V
JV
Department of Paediatrics, School for Oncology and Developmental Biology (GROW), Maastricht University Medical Centre, NL-6202 AZ Maastricht, The Netherlands.
Zoer
Bea
B
Kloosterboer
Nico
N
Kessels
Carolina G A
CG
Zimmermann
Luc J I
LJ
van Iwaarden
J Freek
JF
Villamor
Eduardo
E
D000818:Animals; D001835:Body Weight / Q000502:physiology; D002642:Chick Embryo; D002645:Chickens / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005224:Fats, Unsaturated / Q000378:metabolism; D005317:Fetal Growth Retardation / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018507:Gene Expression Regulation, Developmental; D000860:Hypoxia / Q000150:complications* / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000254:growth & development / Q000378:metabolism*; D009929:Organ Size; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
D005224:Fats, Unsaturated; D010743:Phospholipids; D020033:Protein Isoforms; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A