Signaling molecules in the fetal rabbit model for congenital diaphragmatic hernia.
OBJECTIVE
Little is known about molecular changes in lungs of fetal rabbits with surgically induced diaphragmatic hernia (DH). Therefore, we examined in this model gene expressions of pivotal molecules for the developing lung.


METHODS
At day 23 of gestation, DH was created in 12 fetuses from 4 does. Both lungs from six live DH fetuses and from six unoperated controls were harvested and weighed at term. Transcription of 15 genes involved in alveolarization, angiogenesis, regulation of vascular tone, or epithelial maturation was investigated by real-time quantitative polymerase chain reaction.


RESULTS
DH decreased lung-to-body weight ratio (P < 0.001). A bilateral downregulation was seen for genes encoding for tropoelastin (P < 0.01), lysyl oxidase (P < 0.05), fibulin 5 (P < 0.05), and cGMP specific phosphodiesterase 5 (P < 0.05). Lower mRNA levels for endothelial nitric oxide synthase occurred in the ipsilateral lung (P < 0.05).


CONCLUSIONS
Experimental DH in fetal rabbits disrupted transcription of genes implicated in lung growth and function. Similarities with the human disease make this model appropriate for investigation of new prenatal therapies.
Laboratory of Physiology and Physiopathology, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium. avuckovi@ulb.ac.be
Aline
A
Vuckovic
Xenia I
XI
Roubliova
Carmela
C
Votino
Robert
R
Naeije
Jacques C
JC
Jani
D000818:Animals; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5 / Q000096:biosynthesis / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D005325:Fetal Organ Maturity / Q000502:physiology; D005333:Fetus / Q000378:metabolism; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006548:Hernia, Diaphragmatic / Q000378:metabolism / Q000601:surgery; D065630:Hernias, Diaphragmatic, Congenital; D006801:Humans; D008168:Lung / Q000254:growth & development* / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis / Q000235:genetics; D011247:Pregnancy; D008249:Protein-Lysine 6-Oxidase / Q000096:biosynthesis / Q000235:genetics; D011817:Rabbits; D015398:Signal Transduction / Q000502:physiology*; D014333:Tropoelastin / Q000096:biosynthesis / Q000235:genetics
D014333:Tropoelastin; D052250:Nitric Oxide Synthase Type III; D008249:Protein-Lysine 6-Oxidase; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5