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dc.contributor.authorKoel, Mariann
dc.contributor.authorVargas, Eva
dc.contributor.authorSola Leyva, Alberto 
dc.contributor.authorAltmae, Signe 
dc.date.accessioned2022-12-02T12:58:12Z
dc.date.available2022-12-02T12:58:12Z
dc.date.issued2022-10-13
dc.identifier.citationMariann Koel... [et al.]. Human endometrial cell-type-specific RNA sequencing provides new insights into the embryo–endometrium interplay, Human Reproduction Open, Volume 2022, Issue 4, 2022, hoac043, [https://doi.org/10.1093/hropen/hoac043]es_ES
dc.identifier.urihttps://hdl.handle.net/10481/78261
dc.description.abstractSTUDY QUESTION: Which genes regulate receptivity in the epithelial and stromal cellular compartments of the human endometrium, and which molecules are interacting in the implantation process between the blastocyst and the endometrial cells? SUMMARY ANSWER: A set of receptivity-specific genes in the endometrial epithelial and stromal cells was identified, and the role of galectins (LGALS1 and LGALS3), integrin b1 (ITGB1), basigin (BSG) and osteopontin (SPP1) in embryo–endometrium dialogue among many other protein–protein interactions were highlighted. WHAT IS KNOWN ALREADY: The molecular dialogue taking place between the human embryo and the endometrium is poorly understood due to ethical and technical reasons, leaving human embryo implantation mostly uncharted. STUDY DESIGN, SIZE, DURATION: Paired pre-receptive and receptive phase endometrial tissue samples from 16 healthy women were used for RNA sequencing. Trophectoderm RNA sequences were from blastocysts. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cell-type-specific RNA-seq analysis of freshly isolated endometrial epithelial and stromal cells using fluorescence-activated cell sorting (FACS) from 16 paired pre-receptive and receptive tissue samples was performed. Endometrial transcriptome data were further combined in silico with trophectodermal gene expression data from 466 single cells originating from 17 blastocysts to characterize the first steps of embryo implantation. We constructed a protein–protein interaction network between endometrial epithelial and embryonal trophectodermal cells, and between endometrial stromal and trophectodermal cells, thereby focusing on the very first phases of embryo implantation, and highlighting the molecules likely to be involved in the embryo apposition, attachment and invasion. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 499 epithelial and 581 stromal genes were up-regulated in the receptive phase endometria when compared to pre-receptive samples. The constructed protein–protein interactions identified a complex network of 558 prioritized protein–protein interactions between trophectodermal, epithelial and stromal cells, which were grouped into clusters based on the function of the involved molecules. The role of galectins (LGALS1 and LGALS3), integrin b1 (ITGB1), basigin (BSG) and osteopontin (SPP1) in the embryo implantation process were highlighted. LARGE SCALE DATA: RNA-seq data are available at www.ncbi.nlm.nih.gov/geo under accession number GSE97929. LIMITATIONS, REASONS FOR CAUTION: Providing a static snap-shot of a dynamic process and the nature of prediction analysis is limited to the known interactions available in databases. Furthermore, the cell sorting technique used separated enriched epithelial cells and stromal cells but did not separate luminal from glandular epithelium. Also, the use of biopsies taken from non-pregnant women and using spare IVF embryos (due to ethical considerations) might miss some of the critical interactions characteristic of natural conception only. WIDER IMPLICATIONS OF THE FINDINGS: The findings of our study provide new insights into the molecular embryo–endometrium interplay in the first steps of implantation process in humans. Knowledge about the endometrial cell-type-specific molecules that coordinate successful implantation is vital for understanding human reproduction and the underlying causes of implantation failure and infertility. Our study results provide a useful resource for future reproductive research, allowing the exploration of unknown mechanisms of implantation. We envision that those studies will help to improve the understanding of the complex embryo implantation process, and hopefully generate new prognostic and diagnostic biomarkers and therapeutic approaches to target both infertility and fertility, in the form of new contraceptives.es_ES
dc.description.sponsorshipEstonian Research Council PRG1076es_ES
dc.description.sponsorshipHorizon 2020 innovation grant (ERIN) EU952516es_ES
dc.description.sponsorshipEnterprise Estonia EU48695es_ES
dc.description.sponsorshipEU-FP7 Marie Curie Industry-Academia Partnerships and Pathways (IAPP) EU324509es_ES
dc.description.sponsorshipSpanish Governmentes_ES
dc.description.sponsorshipEuropean Commission RYC-2016-21199 ENDORE SAF2017-87526-R PID2021-127280OB-100es_ES
dc.description.sponsorshipPrograma Operativo FEDER Andalucia B-CTS-500-UGR18 A-CTS-614-UGR20es_ES
dc.description.sponsorshipJunta de Andalucia PAIDI P20_00158es_ES
dc.description.sponsorshipMargarita Salas program for the Requalification of the Spanish University system UJAR01MSes_ES
dc.description.sponsorshipKnut & Alice Wallenberg Foundation KAW 2015.0096es_ES
dc.description.sponsorshipSwedish Research Counciles_ES
dc.description.sponsorshipEuropean Commission 2012-2844es_ES
dc.description.sponsorshipSigrid Juselius Foundationes_ES
dc.description.sponsorshipAcademy of Finlandes_ES
dc.description.sponsorshipSpanish Government PRE2018-085440es_ES
dc.language.isoenges_ES
dc.publisherOxford University Presses_ES
dc.rightsAtribución-NoComercial 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/*
dc.subjectBlastocystes_ES
dc.subjectEndometrial epitheliumes_ES
dc.subjectEmbryo implantationes_ES
dc.subjectEndometrial receptivityes_ES
dc.subjectEndometrial stromaes_ES
dc.subjectInteractomees_ES
dc.titleHuman endometrial cell-type-specific RNA sequencing provides new insights into the embryo–endometrium interplayes_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/H2020/952516es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7/324509es_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES
dc.identifier.doi10.1093/hropen/hoac043
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersiones_ES


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