ArticleHuman reproduction open2026
Altered miRNA cargo of endometrial extracellular vesicles in patients with endometriosis: potential implications for pregnancy outcomes.
Article in Human reproduction open, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
study questionCould the miRNA cargo of extracellular vesicles (EVs) secreted by eutopic endometrium from women with endometriosis be involved in the pregnancy complications related to endometriosis? SUMMARY ANSWER: EVs secreted by eutopic endometrium from women with endometriosis present altered miRNA that modulates biological processes related to pregnancy disorders. WHAT IS KNOWN ALREADY: Communication between endometrial cells, immune cells, endothelial cells, and the embryo is essential for the correct establishment and development of pregnancy, and EVs have been proposed as key mediators of this dialogue. This study aimed to elucidate whether EV-mediated communication is altered in endometriosis, by analysing the miRNA cargo of EVs secreted by eutopic endometrium from women with endometriosis, after differentiation to the gestational phase, compared with the miRNA cargo of EVs secreted by eutopic endometrium from healthy women, also after differentiation to the gestational phase. STUDY DESIGN SIZE DURATION: This was a prospective experimental comparative study in which endometrial organoids were derived from eutopic endometrium of patients with endometriosis (n = 16) and healthy women (n = 15). PARTICIPANTS/MATERIALS SETTING
methodsOrganoids were differentiated to mimic the gestational phase through supplementation with pregnancy hormones. EVs were then isolated from the culture medium, characterized, and their miRNA cargo was profiled by sequencing. Target genes of the significantly differentially expressed miRNAs were identified, and functional enrichment analysis was subsequently performed. Finally, the organoids were co-cultured with human endometrial stromal cells (hESCs) and human placental choriocarcinoma JAR cells, and the effects of EV-derived miRNAs were assessed by qPCR using representative target genes selected based on their roles in endometrium-embryo communication and epithelial-mesenchymal and mesenchymal-epithelial transitions (EMT-MET) in organoids, EMT in stromal (hESC) cells, and endometrium-embryo communication in JAR cells. MAIN RESULTS AND THE ROLE OF CHANCE: EVs were successfully isolated. miRNA-seq showed eight significantly differentially expressed miRNAs (false discovery rate [FDR] < 0.05); six were downregulated: miR-1290, miR-1246, miR-320d, miR-4516, miR-12136, and miR-3065-5p; and two were upregulated: miR-191-5p, and miR-335-5p. These miRNAs target 3964 genes and GO enrichment analysis identified 789 biological processes (FDR < 0.05), mainly involved in embryo development and developmental growth, immune system function, angiogenesis, and epithelial-mesenchymal transition. KEGG pathway analysis revealed 32 deregulated pathways (FDR < 0.05), including the PI3K-Akt pathway commonly related to the pathogenesis of preeclampsia. Validation in gestational epithelial endometriosis organoids showed upregulation of LARGE SCALE DATA: All raw sequencing data are available through the Gene Expression Omnibus (GEO) under accession number GSE302961. LIMITATIONS REASONS FOR CAUTION: This was an WIDER IMPLICATIONS OF THE
findingsEVs secreted by eutopic endometrium from women with endometriosis present altered miRNA that modulates processes essential for a successful pregnancy and could serve as potential diagnostic biomarkers for endometriosis and pregnancy disorders. These results also open avenues for further research about potential targets to promote pregnancy success in women with endometriosis. STUDY FUNDING/COMPETING INTERESTS: This study was supported by the Spanish Ministry of Education through FPU (FPU21/00988 awarded to A.M.-P.), the Carlos III Health Institute, and cofounded by the European Social Fund (ESF) 'Investing in your future' through PI21/00184 and PI24/00961 (awarded to H.F.) and F122/00102 (awarded to A.B.-R.), a Sara Borrell Contract (CD23/00157 awarded to A.C. and CD24/00184 awarded to A.V.), and Miguel Servet Programme grants (CP20/00120 awarded to H.F. and CP19/00149 awarded to I.C.). This study was also supported by Fundació La Marató de TV3 (12/C/2024). The authors have no conflicts of interest to disclose.
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