title: Pulmonary transcriptome analysis in the surgically induced rabbit model of diaphragmatic hernia treated with fetal tracheal occlusion.
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.
authors.affiliation: Department 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.
authors.forename: Alexander C
authors.initials: AC
authors.lastname: Engels
authors.affiliation: Department of Human Genetics, Centre for Human Genetics, University Hospitals KU Leuven, 3000 Leuven, Belgium.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Brady
authors.affiliation: Department of Human Genetics, Centre for Human Genetics, University Hospitals KU Leuven, 3000 Leuven, Belgium.
authors.forename: Molka
authors.initials: M
authors.lastname: Kammoun
authors.affiliation: Department of Human Genetics, Centre for Human Genetics, University Hospitals KU Leuven, 3000 Leuven, Belgium.
authors.forename: Julio
authors.initials: J
authors.lastname: Finalet Ferreiro
authors.affiliation: Department 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.
authors.forename: Philip
authors.initials: P
authors.lastname: DeKoninck
authors.affiliation: Department of Development and Regeneration, Organ System Cluster, Faculty of Medicine, KU Leuven, 3000 Leuven, Belgium.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Endo
authors.affiliation: Department 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.
authors.forename: Jaan
authors.initials: J
authors.lastname: Toelen
authors.affiliation: Department of Human Genetics, Centre for Human Genetics, University Hospitals KU Leuven, 3000 Leuven, Belgium.
authors.forename: Joris R
authors.initials: JR
authors.lastname: Vermeesch
authors.affiliation: Department 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.
authors.forename: Jan
authors.initials: J
authors.lastname: Deprest
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D065630:Hernias, Diaphragmatic, Congenital / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D008168:Lung / Q000378:metabolism*; D011817:Rabbits; D014132:Trachea / Q000196:embryology*; D059467:Transcriptome
keywords: CDH; Congenital diaphragmatic hernia; Fetoscopy; Pulmonary hypoplasia; RNA-seq; Tracheal occlusion