Pulmonary transcriptome analysis in the rabbit model of surgically-induced diaphragmatic hernia treated with fetal tracheal occlusion
Author(s) -
Alexander Engels,
Paul Brady,
Molka Kammoun,
José Luis Ferreiro,
Philip DeKoninck,
Masayuki Endo,
Jaan Toelen,
Joris Vermeesch,
Jan Deprest
Publication year - 2016
Publication title -
disease models and mechanisms
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.327
H-Index - 83
eISSN - 1754-8411
pISSN - 1754-8403
DOI - 10.1242/dmm.021626
Subject(s) - congenital diaphragmatic hernia , pulmonary hypoplasia , fetus , transcriptome , in utero , occlusion , fetal surgery , diaphragmatic hernia , hypoplasia , diaphragmatic breathing , medicine , gene expression , gene , hernia , andrology , biology , pathology , anatomy , surgery , pregnancy , genetics , alternative medicine
Congenital diaphragmatic hernia (CDH) is a malformation leading to pulmonary hypoplasia, which can be treated in utero by fetal tracheal occlusion (TO). However, the changes of gene expression induced by TO remain largely unknown but could be used to further improve the clinically used prenatal treatment of this devastating malformation. Therefore, we aimed to investigate the pulmonary transcriptome changes caused by surgical induction of diaphragmatic hernia (DH) and additional TO in the fetal rabbit model. Induction of DH was associated with 378 upregulated genes compared to controls when allowing a false-discovery rate (FDR) of 0.1 and a fold change (FC) of 2. Those genes were again downregulated by consecutive TO. But DH+TO was associated with an upregulation of 157 genes compared to DH and controls. When being compared to control lungs, 106 genes were downregulated in the DH group and were not changed by TO. Therefore, the overall pattern of gene expression in DH+TO is more similar to the control group than to the DH group. In this study, we further provide a database of gene expression changes induced by surgical creation of DH and consecutive TO in the rabbit model. Future treatment strategies could be developed using this dataset. We also discuss the most relevant genes that are involved in CDH.
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