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Ministerio de Ciencia e Innovaci\u00f3n.","award":["ACIF\/2019\/139"],"award-info":[{"award-number":["ACIF\/2019\/139"]}]},{"name":"European Social Fund (ESF) \u201cInvesting in your future\u201d through the Miguel Servet Program","award":["CP19\/00149"],"award-info":[{"award-number":["CP19\/00149"]}]},{"name":"European Social Fund (ESF) \u201cInvesting in your future\u201d through the Miguel Servet Program","award":["CP20\/00120"],"award-info":[{"award-number":["CP20\/00120"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Reprod Biol Endocrinol"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Women with adenomyosis are characterized by having defective decidualization, impaired endometrial receptivity and\/or embryo-maternal communication, and implantation failure. However, the molecular mechanisms underlying adenomyosis-related infertility remain unknown, mainly because of the restricted accessibility and the difficult preservation of endometrial tissue in vitro. We have recently shown that adenomyosis patient-derived endometrial organoids, maintain disease-specific features while differentiated into mid-secretory and gestational endometrial phase, overcoming these research barriers and providing a robust platform to study adenomyosis pathogenesis and the associated molecular dysregulation related to implantation and pregnancy disorders. For this reason, we aim to characterize the dysregulated mechanisms in the mid-secretory and gestational endometrium of patients with adenomyosis by RNA-sequencing.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Endometrial organoids were derived from endometrial biopsies collected in the proliferative phase of women with adenomyosis (ADENO) or healthy oocyte donors (CONTROL) (n\u2009=\u200915\/group) and differentiated into mid-secretory (-SECorg) and gestational (-GESTorg) phases in vitro. Following RNA-sequencing, the significantly differentially expressed genes (DEGs) (FDR\u2009&lt;\u20090.05) were identified and selected for subsequent functional enrichment analysis and QIAGEN Ingenuity Pathway Analysis (IPA). Statistical differences in gene expression were evaluated with the Student\u2019s t-test or Wilcoxon test.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>We identified 1,430 DEGs in ADENO-SECorg and 1,999 DEGs in ADENO-GESTorg. In ADENO-SECorg, upregulated genes included <jats:italic>OLFM1<\/jats:italic>, <jats:italic>FXYD5<\/jats:italic>, and <jats:italic>RUNX2<\/jats:italic>, which are involved in impaired endometrial receptivity and implantation failure, while downregulated genes included <jats:italic>RRM2, SOSTDC1<\/jats:italic>, and <jats:italic>CHAC2<\/jats:italic> implicated in recurrent implantation failure. In ADENO-GESTorg, upregulated <jats:italic>CXCL14<\/jats:italic> and <jats:italic>CYP24A1<\/jats:italic> and downregulated <jats:italic>PGR<\/jats:italic> were related to pregnancy loss. IPA predicted a significant inhibition of ID1 signaling, histamine degradation, and activation of HMGB1 and Senescence pathways, which are related to implantation failure. Alternatively, IPA predicted an inhibition of D-myo-inositol biosynthesis and VEGF signaling, and upregulation of Rho pathway, which are related to pregnancy loss and preeclampsia.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Identifying dysregulated molecular mechanisms in mid-secretory and gestational endometrium of adenomyosis women contributes to the understanding of adenomyosis-related implantation failure and\/or pregnancy disorders revealing potential therapeutic targets. Following experimental validation of our transcriptomic and <jats:italic>in silico<\/jats:italic> findings, our differentiated adenomyosis patient-derived organoids have the potential to provide a reliable platform for drug discovery, development, and personalized drug screening for affected patients.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12958-023-01182-7","type":"journal-article","created":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T06:02:46Z","timestamp":1704780166000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Transcriptome analysis of adenomyosis eutopic endometrium reveals molecular mechanisms involved in adenomyosis-related implantation failure and pregnancy disorders"],"prefix":"10.1186","volume":"22","author":[{"given":"Elena","family":"Ju\u00e1rez-Barber","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Corach\u00e1n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Cristina","family":"Carbajo-Garc\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amparo","family":"Faus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Vidal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Giles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Pellicer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Cervell\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hortensia","family":"Ferrero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,1,9]]},"reference":[{"key":"1182_CR1","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1080\/17446651.2019.1697675","volume":"14","author":"P Vercellini","year":"2019","unstructured":"Vercellini P, Bonfanti I, Berlanda N. 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