Abstract

Endometriosis is a common gynaecological disease of women in reproductive age, and is thought to arise from retrograde menstruation and implantation of endometrial tissue, mostly into the peritoneal cavity. The condition is characterized by a chronic, unresolved inflammatory process thereby contributing to pain as cardinal symptom in endometriosis. Elevated reactive oxygen species (ROS) and oxidative stress have been postulated as factors in endometriosis pathogenesis. We here set out for a systematic study to identify novel mechanisms and pathways relating to oxidative stress in ectopic peritoneal lesions. Using combined proteomic and transcriptomic approaches, we identified novel targets including upregulated pro-oxidative enzymes, such as amine oxidase 3/vascular adhesion protein 1 (AOC3/VAP1) as well as downregulated protective factors, in particular alkenal reductase PTGR1 and methionine sulfoxide reductase. Consistent with an altered ROS landscape, we observed hemoglobin / iron overload, ROS production and lipid peroxidation in ectopic lesions. ROS-derived 4-hydroxy-2-nonenal induced interleukin IL-8 release from monocytes. Notably, AOC3 inhibitors provoked analgesic effects in inflammatory pain models in vivo, suggesting potential translational applicability.

Details

Title
Amine oxidase 3 is a novel pro-inflammatory marker of oxidative stress in peritoneal endometriosis lesions
Author
Marie-Laëtitia, Thézénas 1 ; De Leo Bianca 2 ; Laux-Biehlmann Alexis 2 ; Cemsel, Bafligil 3   VIAFID ORCID Logo  ; Elger Bernd 2 ; Tapmeier, Thomas 4   VIAFID ORCID Logo  ; Karl, Morten 4 ; Rahmioglu Nilufer 5 ; Dakin, Stephanie G 3 ; Charles, Philip 1   VIAFID ORCID Logo  ; Martinez Fernando Estrada 3 ; Steers, Graham 6 ; Fischer, Oliver M 2 ; Mueller, Joerg 2 ; Hess-Stumpp, Holger 2 ; Steinmeyer, Andreas 2 ; Manek Sanjiv 4 ; Zondervan, Krina T 5   VIAFID ORCID Logo  ; Kennedy, Stephen 6 ; Becker, Christian M 6   VIAFID ORCID Logo  ; Shang, Catherine 7 ; Zollner, Thomas M 2 ; Kessler, Benedikt M 1   VIAFID ORCID Logo  ; Oppermann Udo 8   VIAFID ORCID Logo 

 University of Oxford, Target Discovery Institute, Nuffield Department of Medicine, Oxford, UK (GRID:grid.4991.5) (ISNI:0000 0004 1936 8948) 
 Bayer AG, R&D, Gynaecological Therapies, Berlin, Germany (GRID:grid.491576.8) 
 University of Oxford, Botnar Research Centre, NIHR Biomedical Research Unit Oxford, Nuffield Department of Musculoskeletal Sciences, Oxford, UK (GRID:grid.4991.5) (ISNI:0000 0004 1936 8948) 
 Endometriosis CaRe Centre, Nuffield Department of Obstetrics & Gynaecology, Oxford, UK (GRID:grid.491576.8) 
 Endometriosis CaRe Centre, Nuffield Department of Obstetrics & Gynaecology, Oxford, UK (GRID:grid.491576.8); University of Oxford, Wellcome Trust Centre for Human Genetics, Oxford, UK (GRID:grid.4991.5) (ISNI:0000 0004 1936 8948) 
 Endometriosis CaRe Centre, Nuffield Department of Obstetrics & Gynaecology, Oxford, UK (GRID:grid.4991.5) 
 University of Oxford, Botnar Research Centre, NIHR Biomedical Research Unit Oxford, Nuffield Department of Musculoskeletal Sciences, Oxford, UK (GRID:grid.4991.5) (ISNI:0000 0004 1936 8948); Endometriosis CaRe Centre, Nuffield Department of Obstetrics & Gynaecology, Oxford, UK (GRID:grid.4991.5) 
 University of Oxford, Botnar Research Centre, NIHR Biomedical Research Unit Oxford, Nuffield Department of Musculoskeletal Sciences, Oxford, UK (GRID:grid.4991.5) (ISNI:0000 0004 1936 8948); University of Freiburg, Freiburg Institute for Advanced Studies (FRIAS), Freiburg, Germany (GRID:grid.5963.9) 
Publication year
2020
Publication date
2020
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2348777445
Copyright
This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.