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Extracellular vesicles secreted by adenomyosis endometrial organoids contain miRNAs involved in embryo implantation and pregnancy.
Reprod Biomed Online. 2023 03; 46(3):470-481.RB

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.

Links

Publisher Full Text (DOI)

Authors+Show Affiliations

Juárez-Barber E
Fundación IVI, Instituto de Investigación Sanitaria La Fe, 46026 Valencia, Spain.
Segura-Benítez M
Fundación IVI, Instituto de Investigación Sanitaria La Fe, 46026 Valencia, Spain; Departamento de Pediatría, Obstetricia y Ginecología, Universidad de Valencia, 46010 Valencia, Spain.
Carbajo-García MC
Fundación IVI, Instituto de Investigación Sanitaria La Fe, 46026 Valencia, Spain; Departamento de Pediatría, Obstetricia y Ginecología, Universidad de Valencia, 46010 Valencia, Spain.
Bas-Rivas A
Fundación IVI, Instituto de Investigación Sanitaria La Fe, 46026 Valencia, Spain.
Faus A
Fundación IVI, Instituto de Investigación Sanitaria La Fe, 46026 Valencia, Spain.
Vidal C
Fundación IVI, Instituto de Investigación Sanitaria La Fe, 46026 Valencia, Spain; IVI-RMA Valencia, 46015 Valencia, Spain.
Giles J
Fundación IVI, Instituto de Investigación Sanitaria La Fe, 46026 Valencia, Spain; IVI-RMA Valencia, 46015 Valencia, Spain.
Labarta E
Fundación IVI, Instituto de Investigación Sanitaria La Fe, 46026 Valencia, Spain; IVI-RMA Valencia, 46015 Valencia, Spain.
Pellicer A
Fundación IVI, Instituto de Investigación Sanitaria La Fe, 46026 Valencia, Spain; IVI-RMA Rome, 00197 Rome, Italy.
Cervelló I
Fundación IVI, Instituto de Investigación Sanitaria La Fe, 46026 Valencia, Spain.
Ferrero H
Fundación IVI, Instituto de Investigación Sanitaria La Fe, 46026 Valencia, Spain. Electronic address: hortensia.ferrero@ivirma.com.

MeSH

PregnancyHumansFemaleAbortion, SpontaneousAdenomyosisMicroRNAsEndometriumEmbryo ImplantationExtracellular VesiclesDNA-Binding ProteinsTranscription FactorsRNA-Binding ProteinsProto-Oncogene ProteinsCell Cycle Proteins

Pub Type(s)

Journal Article

Language

eng

PubMed ID

36697316

Citation

Juárez-Barber, Elena, et al. "Extracellular Vesicles Secreted By Adenomyosis Endometrial Organoids Contain miRNAs Involved in Embryo Implantation and Pregnancy." Reproductive Biomedicine Online, vol. 46, no. 3, 2023, pp. 470-481.
Juárez-Barber E, Segura-Benítez M, Carbajo-García MC, et al. Extracellular vesicles secreted by adenomyosis endometrial organoids contain miRNAs involved in embryo implantation and pregnancy. Reprod Biomed Online. 2023;46(3):470-481.
Juárez-Barber, E., Segura-Benítez, M., Carbajo-García, M. C., Bas-Rivas, A., Faus, A., Vidal, C., Giles, J., Labarta, E., Pellicer, A., Cervelló, I., & Ferrero, H. (2023). Extracellular vesicles secreted by adenomyosis endometrial organoids contain miRNAs involved in embryo implantation and pregnancy. Reproductive Biomedicine Online, 46(3), 470-481. https://doi.org/10.1016/j.rbmo.2022.12.008
Juárez-Barber E, et al. Extracellular Vesicles Secreted By Adenomyosis Endometrial Organoids Contain miRNAs Involved in Embryo Implantation and Pregnancy. Reprod Biomed Online. 2023;46(3):470-481. PubMed PMID: 36697316.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Extracellular vesicles secreted by adenomyosis endometrial organoids contain miRNAs involved in embryo implantation and pregnancy. AU - Juárez-Barber,Elena, AU - Segura-Benítez,Marina, AU - Carbajo-García,María Cristina, AU - Bas-Rivas,Alba, AU - Faus,Amparo, AU - Vidal,Carmen, AU - Giles,Juan, AU - Labarta,Elena, AU - Pellicer,Antonio, AU - Cervelló,Irene, AU - Ferrero,Hortensia, Y1 - 2022/12/18/ PY - 2022/10/06/received PY - 2022/12/02/revised PY - 2022/12/13/accepted PY - 2023/1/26/pubmed PY - 2023/3/8/medline PY - 2023/1/25/entrez KW - Adenomyosis KW - Extracellular vesicles KW - Infertility KW - Patient-derived Organoids KW - miRNAs SP - 470 EP - 481 JF - Reproductive biomedicine online JO - Reprod Biomed Online VL - 46 IS - 3 N2 - 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. SN - 1472-6491 UR - https://www.unboundmedicine.com/medline/citation/36697316/Extracellular_vesicles_secreted_by_adenomyosis_endometrial_organoids_contain_miRNAs_involved_in_embryo_implantation_and_pregnancy_ DB - PRIME DP - Unbound Medicine ER -