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Published on: October 19, 2013
Hypoxia-induced intrauterine growth retardation: effects on pulmonary development and surfactant protein
L Gortner1, A Hilgendorff, T Bähner
1Department of Pediatrics and Neonatology, University of Saarland, Homburg/Saar, Germany. kilgor@uniklinik-saarland.de
Insights
Hypoxia-induced intrauterine growth restriction (IUGR) in mice significantly reduced surfactant protein gene expression, impacting lung development. This finding suggests a link between altered surfactant production and pulmonary issues in preterm infants with IUGR.
Area of Science:
- Perinatal medicine
- Developmental biology
- Pulmonary research
Background:
- Intrauterine growth retardation (IUGR) in preterm infants increases the risk of pulmonary disorders like bronchopulmonary dysplasia (BPD).
- A reproducible animal model using hypoxia was established to study IUGR's effects on fetal lung development.
Purpose of the Study:
- To investigate the impact of IUGR, induced by maternal hypoxia, on pulmonary development and maturation in a mouse model.
- To assess changes in somatic growth and surfactant protein gene expression.
Main Methods:
- Mice were exposed to hypoxia (FiO2 0.10) from day 14 to 17.5 of gestation, with a normoxic control group.
- Somatic growth parameters were measured, and histomorphometric analyses of lung tissue were performed.
- Quantitative rt-PCR was used to determine the mRNA expression of surfactant proteins (SP-A, -B, -C, -D).
Main Results:
- Hypoxic fetuses exhibited significantly reduced birth weight, body length, and fronto-occipital diameter compared to controls.
- Histomorphometric analysis showed no significant differences in lung tissue structure between groups.
- mRNA expression of SP-A, SP-B, and SP-C was significantly decreased in hypoxic fetuses, while SP-D expression remained unchanged.
Conclusions:
- Maternal hypoxia during late gestation induces IUGR in preterm mice, altering the developing surfactant system.
- Reduced surfactant protein gene expression is a key finding, potentially contributing to pulmonary complications in IUGR infants.
- This model highlights the critical role of the surfactant system in IUGR-related pulmonary disorders.
Background And Objectives:
Preterm infants with intrauterine growth retardation (IUGR) reveal an increased risk for the development of acute and chronic pulmonary disorders, i.e. bronchopulmonary dysplasia (BPD). In order to investigate the effect of IUGR on pulmonary development, an easily reproducible animal model for fetal growth restriction has been established using hypoxia as a sole intervention in the last third of pregnancy.
Methods:
Date-mated mice were randomly assigned to either being kept at a fraction of inspired oxygen (FiO2) of 0.10 (hypoxic group) starting at day 14 or under normoxic conditions until day 17.5 of gestation (control group). Variables of somatic growth were assessed and standardized histomorphometric analyses of pulmonary tissue were performed. Expression of surfactant proteins (SP)-A, -B, -C and -D was determined by quantitative rt-PCR as biochemical indicators for lung development and maturation.
Results:
Fetuses were delivered preterm at 0.87 of gestation. Those grown under hypoxic conditions revealed significantly lower birth weights (median: 0.69 vs. 0.97 g in controls; p < 0.001), body lengths (median: 17.5 vs. 20.2 mm in controls; p < 0.001) and fronto-occipital diameters (median: 9.4 vs. 10.1 mm in controls; p < 0.001) compared to controls. Histomorphometric analyses were found to be without significant differences between both groups. On the transcriptional level, however, mRNA expression of SP-A, -B and -C but not SP-D could be shown to be significantly reduced in hypoxic fetuses compared to normoxic controls.
Conclusions:
In conclusion, hypoxic conditions from day 14 to 17.5 led to IUGR in preterm mice and to significant alterations of the developing surfactant system. We speculate restricted development of SP gene expression to be a causal factor for the increased risk of acute and chronic pulmonary disorders in preterm infants with IUGR.
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