Dataset Information

Altered inflammatory and pro-angiogenic responses caused by imbalanced protection against oxidative stress in endometriosis

ABSTRACT: Endometriosis is a common gynecological disease of women in reproductive age, and is primarily thought to arise from retrograde menstruation and implantation of endometrium, mostly into the peritoneal cavity. The condition is characterized by a chronic, unresolved inflammatory process, within which oxidative stress likely plays a critical role. Although elevated reactive oxygen species (ROS) and oxidative stress have previously been postulated as being involved in endometriosis pathogenesis, we set out for a more systematic study to identify novel factors defining 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 such as alkenal reductase PTGR1 or methionine sulfoxide reductase, supporting the observation of increased oxidative protein modification in ectopic lesions and peritoneal fluid. The observed ROS-derived 4-hydroxy-2-nonenal-induced interleukin (IL)-8 release from monocytes indicates a further pathomechanism, whereby elevated IL-8 levels promote further immune cell infiltration and angiogenesis in lesions.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Uterine Endometrium

SUBMITTER: Marie-Laëtitia Thézénas

LAB HEAD: Professor Benedikt Kessler

PROVIDER: PXD006553 | Pride | 2020-05-26

REPOSITORIES: Pride

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Publications

Amine oxidase 3 is a novel pro-inflammatory marker of oxidative stress in peritoneal endometriosis lesions.

Thézénas Marie-Laëtitia ML De Leo Bianca B Laux-Biehlmann Alexis A Bafligil Cemsel C Elger Bernd B Tapmeier Thomas T Morten Karl K Rahmioglu Nilufer N Dakin Stephanie G SG Charles Philip P Martinez Fernando Estrada FE Steers Graham G Fischer Oliver M OM Mueller Joerg J Hess-Stumpp Holger H Steinmeyer Andreas A Manek Sanjiv S Zondervan Krina T KT Kennedy Stephen S Becker Christian M CM Shang Catherine C Zollner Thomas M TM Kessler Benedikt M BM Oppermann Udo U

Scientific reports 20200130 1

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 syst ...[more]

PMID: 32001775

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Project description:The pathophysiology of endometriotic lesion development remains unclear but involves a complex interaction between ectopic endometrium and host peritoneal tissues. We hypothesised that disruption of this interaction was likely to suppress endometriotic lesion formation. We hoped to delineate the molecular and cellular dialogue between ectopic human endometrium and peritoneal tissues in nude mice, as a first step towards testing this hypothesis. Human endometrium was xenografted into nude mice and the resulting lesions were analysed using microarrays. A novel technique was developed that unambiguously determined whether RNA transcripts identified by the microarray analyses originated from human cells (endometrium) or mouse cells (stroma). Four key pathways (ubiquitin/proteosome, inflammation, tissue remodelling/repair and ras-mediated oncogenesis) were revealed, that demonstrated communication between host stromal cells and ectopic endometrium. Morphometric analysis of nude mouse lesions confirmed that necrosis, inflammation, healing and repair and cell proliferation occurred during xenograft development. These processes were entirely consistent with the molecular networks revealed by the microarray data. The transcripts detected in the xenografts overlapped with transcripts differentially expressed in a comparison between paired eutopic and ectopic endometrium from human endometriotic patients. For the first time components of the interaction between ectopic endometrium and peritoneal stromal tissues have been revealed in ectopic endometrial lesions. Targeted disruption of this dialogue is likely to disrupt endometriotic tissue formation and may prove to be an effective therapeutic strategy for endometriosis. Experiment Overall Design: Xenografts of human endometrium in nude mice hybridised to both human and mouse specific genechips. 2 biological replicates, at 3 time points. Control human endometrium and mouse pertioneum were hybridised to both human and mouse genechips

Dataset Information

Altered inflammatory and pro-angiogenic responses caused by imbalanced protection against oxidative stress in endometriosis

Publications

Amine oxidase 3 is a novel pro-inflammatory marker of oxidative stress in peritoneal endometriosis lesions.

Similar Datasets

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