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MicroRNA expression profile in endometriosis: its relation to angiogenesis and fibrinolytic factors

STUDY QUESTION Could an aberrant microRNA (miRNA) expression profile be responsible for the changes in the angiogenic and fibrinolytic states observed in endometriotic lesions? SUMMARY ANSWER This study revealed characteristic miRNA expression profiles associated with endometriosis in endometrial ti...

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Published in:Human reproduction (Oxford) 2014-05, Vol.29 (5), p.978-988
Main Authors: Braza-Boïls, Aitana, Marí-Alexandre, Josep, Gilabert, Juan, Sánchez-Izquierdo, Dolors, España, Francisco, Estellés, Amparo, Gilabert-Estellés, Juan
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Language:English
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Summary:STUDY QUESTION Could an aberrant microRNA (miRNA) expression profile be responsible for the changes in the angiogenic and fibrinolytic states observed in endometriotic lesions? SUMMARY ANSWER This study revealed characteristic miRNA expression profiles associated with endometriosis in endometrial tissue and endometriotic lesions from the same patient and their correlation with the most important angiogenic and fibrinolytic factors. WHAT IS ALREADY KNOWN? An important role for dysregulated miRNA expression in the pathogenesis of endometriosis is well documented. However, to the best of our knowledge, there are no reports of the relationship between angiogenic and fibrinolytic factors and miRNAs when endometrial tissue and different types of endometriotic lesions from the same patient are compared. STUDY DESIGN, SIZE, DURATION Case–control study that involved 51 women with endometriosis and 32 women without the disease (controls). PARTICIPANTS/MATERIALS, SETTING, METHODS The miRNA expression profiles were determined using the GeneChip miRNA 2.0 Affymetrix array platform, and the results were analysed using Partek Genomic Suite software. To validate the obtained results, 12 miRNAs differentially expressed were quantified by using miRCURY LNA™ Universal RT microRNA PCR. Levels of vascular endothelial growth factor (VEGF-A), thrombospondin-1 (TSP-1), urokinase plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) proteins were quantified by ELISA. MAIN RESULTS AND THE ROLE OF CHANCE Patient endometrial tissue showed significantly lower levels of miR-202-3p, miR-424-5p, miR-449b-3p and miR-556-3p, and higher levels of VEGF-A and uPA than healthy (control) endometrium. However, tissue affected by ovarian endometrioma showed significantly lower expression of miR-449b-3p than endometrium from both controls and patients, and higher levels of PAI-1 and the angiogenic inhibitor TSP-1. A significant inverse correlation between miR-424-5p and VEGF-A protein levels was observed in patient endometrium, and an inverse correlation between miR-449b-3p and TSP-1 protein levels was observed in ovarian endometrioma. Peritoneal implants had significantly higher levels of VEGF-A than ovarian endometrioma samples. LIMITATIONS, REASONS FOR CAUTION Functional studies are needed to confirm the specific targets of the miRNAs differently expressed. WIDER IMPLICATIONS OF THE FINDINGS Differences in miRNA levels could modulate the expression of VEGF-A and TSP-1, which
ISSN:0268-1161
1460-2350
DOI:10.1093/humrep/deu019