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Signaling molecules in the fetal rabbit model for congenital diaphragmatic hernia
Author(s) -
Vuckovic Aline,
Roubliova Xenia I.,
Votino Carmela,
Naeije Robert,
Jani Jacques C.
Publication year - 2012
Publication title -
pediatric pulmonology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.866
H-Index - 106
eISSN - 1099-0496
pISSN - 8755-6863
DOI - 10.1002/ppul.22512
Subject(s) - lysyl oxidase , medicine , fetus , tropoelastin , congenital diaphragmatic hernia , lung , angiogenesis , diaphragmatic hernia , downregulation and upregulation , elastin , respiratory disease , endocrinology , pathology , andrology , gene , hernia , biology , surgery , microbiology and biotechnology , extracellular matrix , biochemistry , pregnancy , genetics
Rationale and objectives 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. Main 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. Pediatr Pulmonol. 2012. 47:1088–1096. © 2012 Wiley Periodicals, Inc.