Link: http://www.ncbi.nlm.nih.gov/pubmed/26744354

Dis Model Mech. 2016 Feb 1;9(2):221-8. doi: 10.1242/dmm.021626. Epub 2016 Jan 7.
Pulmonary transcriptome analysis in the surgically induced rabbit model of diaphragmatic hernia treated with fetal tracheal occlusion.
Engels AC1, Brady PD2, Kammoun M2, Finalet Ferreiro J2, DeKoninck P1, Endo M3, Toelen J4, Vermeesch JR2, Deprest J5.
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1Department of Development and Regeneration, Organ System Cluster, Faculty of Medicine, KU Leuven, 3000 Leuven, Belgium Clinical Department of Obstetrics and Gynaecology, Division Woman and Child, University Hospitals KU Leuven, 3000 Leuven, Belgium.
2Department of Human Genetics, Centre for Human Genetics, University Hospitals KU Leuven, 3000 Leuven, Belgium.
3Department of Development and Regeneration, Organ System Cluster, Faculty of Medicine, KU Leuven, 3000 Leuven, Belgium.
4Department of Development and Regeneration, Organ System Cluster, Faculty of Medicine, KU Leuven, 3000 Leuven, Belgium Clinical Department of Pediatrics, Division Woman and Child, University Hospitals KU Leuven, 3000 Leuven, Belgium.
5Department of Development and Regeneration, Organ System Cluster, Faculty of Medicine, KU Leuven, 3000 Leuven, Belgium Clinical Department of Obstetrics and Gynaecology, Division Woman and Child, University Hospitals KU Leuven, 3000 Leuven, Belgium jan.deprest@uzleuven.be.
Abstract
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.
© 2016. Published by The Company of Biologists Ltd.
KEYWORDS:
CDH; Congenital diaphragmatic hernia; Fetoscopy; Pulmonary hypoplasia; RNA-seq; Tracheal occlusion