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Updated: Jun 19, 2026
Isolation of Pulmonary Artery Smooth Muscle Cells from Neonatal Mice
Published on: October 19, 2013
Pulmonary vascular endothelial growth factor expression and disaturated phospholipid content in a chicken model of
Jasper V Been1, Bea Zoer, Nico Kloosterboer
1Department of Paediatrics, School for Oncology and Developmental Biology (GROW), Maastricht University Medical Centre, NL-6202 AZ Maastricht, The Netherlands.
Insights
Prenatal oxygen levels impact fetal lung development. Both hypoxia and hyperoxia alter surfactant production, with vascular endothelial growth factor (VEGF) playing a role in this response.
Area of Science:
- Pulmonary Medicine
- Developmental Biology
- Neonatology
Background:
- Prenatal hypoxia is a known cause of intrauterine growth retardation, impacting fetal lung maturation with conflicting prior study results.
- The fetal chicken model offers a unique system to isolate and study the effects of hypoxia during development.
Purpose of the Study:
- To investigate the hypothesis that prenatal hypoxia differentially affects surfactant synthesis based on the timing and duration of exposure.
- To analyze pulmonary vascular endothelial growth factor (VEGF) expression as a potential mediator linking oxygen sensing to surfactant production.
Main Methods:
- Fertilized White Leghorn eggs were exposed to normoxia, hyperoxia (60% O2), or hypoxia (15% O2) from specific developmental days (day 6 or 15).
- Whole lung disaturated phospholipids (DSPL) and mRNA expression of VEGF isoforms were quantified at days 16 and 19.
Main Results:
- Lung DSPL content significantly increased by day 19 in both hypoxia and hyperoxia groups exposed from day 15, compared to controls.
- Long-term hypoxia exposure showed a trend towards decreased DSPL content, while short-term hypoxia transiently up-regulated VEGF146 at day 16.
- No significant differences in DSPL content were observed at day 16, and VEGF expression changes were transient.
Conclusions:
- Prenatal hypoxia and hyperoxia, when induced during critical lung development windows, differentially modulate surfactant synthesis.
- Fetal oxygen tension serves as a key signaling mechanism in regulating the fetal lung surfactant system.
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.
Objectives:
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.
