Pulmonary transcriptome analysis in the rabbit model of surgically-induced diaphragmatic hernia treated with fetal tracheal occlusion

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 due to surgical induction of diaphragmatic hernia (DH) and additional tracheal occlusion in the fetal rabbit model.Induction of DH was associated with 378 up-regulated 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 down-regulated by consecutive TO. But DH+TO was associated with an up-regulation of 157 genes compared to DH and controls. When being compared to control lungs, 106 genes were down-regulated 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 then 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.

Jaar van publicatie:2016