子宫内膜分泌的细胞外囊泡是否含有与腺肌症相关不孕症有关的miRNA？本研究使用腺肌症女性（n = 4）的正常子宫内膜器官样品生成和分化到分泌期和孕期，并运用下一代测序分析每个阶段分化的器官样品中分泌的细胞外囊泡中的miRNA成分。分别根据计数每百万的标准选择分泌期外囊泡和孕期外囊泡中的miRNA，使用miRNet获取每个阶段miRNA靶向的基因，应用基因本体论进行富集分析。miRNA测序鉴定出分泌期细胞外囊泡中的80个miRNA，包括与腺肌症发病和着床失败有关的hsa-miR-21-5p、hsa-miR-24-3p、hsa-miR-26a-5p、hsa-miR-92a-3p、hsa-miR-92b-3p、hsa-miR-200c-3p和hsa-miR-423a-5p。此外，在孕期细胞外囊泡中鉴定出60个miRNA，包括与妊娠高血压和流产有关的hsa-miR-21-5p、hsa-miR-26a-5p、hsa-miR-30a-5p、hsa-miR-30c-5p、hsa-miR-222-3p和hsa-miR-423a-5p。这些miRNA的靶向基因包括PTEN、MDM4、PLAGL2和CELF1，它们的下调（分别是P = 0.0003、P < 0.0001、P = 0.0002和P = 0.0003）导致腺肌症发病、早期胚胎发育障碍和着床失败和流产。进一步的靶向基因功能富集分析揭示它们参与细胞分化、增殖、凋亡、细胞周期调节和对细胞外刺激的反应。腺肌症女性分泌的细胞外囊泡中含有参与腺肌症进展、胚胎着床障碍和妊娠并发症的miRNA。版权所有©2022生殖保健有限公司。由Elsevier Ltd.出版，版权所有。

Do extracellular vesicles secreted by the endometrium of women with adenomyosis contain miRNAs involved in adenomyosis-related infertility?A descriptive study using organoids from eutopic endometrium of women with adenomyosis (n = 4) generated and differentiated to secretory and gestational phases, in which miRNA cargo from extracellular vesicles secreted by these differentiated organoids in each phase was analysed by next-generation sequencing. miRNAs in secretory-extracellular vesicles and gestational-extracellular vesicles were selected based on the counts per million. miRNAs target genes in each phase were obtained from miRNet and gene ontology was used for enrichment analysis.miRNA sequencing identified 80 miRNAs in secretory-phase extracellular vesicles, including hsa-miR-21-5p, hsa-miR-24-3p, hsa-miR-26a-5p, hsa-miR-92a-3p, hsa-miR-92b-3p, hsa-miR-200c-3p and hsa-miR-423a-5p, related to adenomyosis pathogenesis and implantation failure. Further, 60 miRNAs were identified in gestational-phase extracellular vesicles, including hsa-miR-21-5p, hsa-miR-26a-5p, hsa-miR-30a-5p, hsa-miR-30c-5p, hsa-miR-222-3p and hsa-miR-423a-5p were associated with preeclampsia and miscarriage. Among the target genes of these miRNAs, PTEN, MDM4, PLAGL2 and CELF1, whose downregulation (P = 0.0003, P < 0.0001, P = 0.0002 and P = 0.0003, respectively) contributes to adenomyosis pathogenesis, and impaired early embryo development, leading to implantation failure and miscarriage, are highlihghted. Further, functional enrichment analyses of the target genes revealed their involvement in cell differentiation, proliferation, apoptosis, cell cycle regulation and response to extracellular stimuli.Eutopic endometrium in secretory and gestational phase from women with adenomyosis releases extracellular vesicles containing miRNAs involved in adenomyosis progression, impaired embryo implantation and pregnancy complications.Copyright © 2022 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.