Extracellular vesicles secreted by adenomyosis endometrial organoids contain miRNAs involved in embryo implantation and pregnancy

Elena Juárez‐Barber, Juárez-Barber E, Elena Juárez-Barber, Segura-Benítez M, Marina Segura-Benítez, María Cristina Carbajo‐García, Carbajo-García MC, María Cristina Carbajo-García, Alba Bas-Rivas, Amparo Faus, Faus A, C. Vidal, Carmen Vidal, Giles J, Juan Giles, Juan Gilés, Elena Labarta, Labarta E, Antonio Pellicer, António Pellicer, Pellicer A, Irene Cervelló, Hortensia Ferrero
Reproductive biomedicine online · 2022 · vol. 46(3) , pp. 470–481 · doi:10.1016/j.rbmo.2022.12.008 · PMID:36697316 · W4311966913
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Adenomyosis endometrial organoids secrete extracellular vesicles carrying microRNAs that play roles in embryo implantation and pregnancy.

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Abstract

RESEARCH QUESTION: Do extracellular vesicles secreted by the endometrium of women with adenomyosis contain miRNAs involved in adenomyosis-related infertility? DESIGN: 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. RESULTS: 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. CONCLUSIONS: 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.

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Condition tags

adenomyosis

MeSH descriptors

Abortion, Spontaneous Abortion, Spontaneous Abortion, Spontaneous Abortion, Spontaneous Abortion, Spontaneous Abortion, Spontaneous Abortion, Spontaneous Abortion, Spontaneous Abortion, Spontaneous Abortion, Spontaneous Abortion, Spontaneous Abortion, Spontaneous Abortion, Spontaneous Abortion, Spontaneous Abortion, Spontaneous Abortion, Spontaneous Abortion, Spontaneous Abortion, Spontaneous Abortion, Spontaneous Abortion, Spontaneous

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

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