{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T23:41:31Z","timestamp":1790811691502,"version":"4.1.0"},"reference-count":104,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,2,4]],"date-time":"2022-02-04T00:00:00Z","timestamp":1643932800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["FI19\/00110"],"award-info":[{"award-number":["FI19\/00110"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["CP20\/00120"],"award-info":[{"award-number":["CP20\/00120"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["CP19\/00149"],"award-info":[{"award-number":["CP19\/00149"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003359","name":"Generalitat Valenciana","doi-asserted-by":"publisher","award":["APOSTD\/2020\/123"],"award-info":[{"award-number":["APOSTD\/2020\/123"]}],"id":[{"id":"10.13039\/501100003359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["FPU18\/06327"],"award-info":[{"award-number":["FPU18\/06327"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Adenomyosis is related to infertility and miscarriages, but so far there are no robust in vitro models that reproduce its pathological features to study the molecular mechanisms involved in this disease. Endometrial organoids are in vitro 3D models that recapitulate the native microenvironment and reproduce tissue characteristics that would allow the study of adenomyosis pathogenesis and related infertility disorders. In our study, human endometrial biopsies from adenomyosis (n = 6) and healthy women (n = 6) were recruited. Organoids were established and hormonally differentiated to recapitulate midsecretory and gestational endometrial phases. Physiological and pathological characteristics were evaluated by immunohistochemistry, immunofluorescence, qRT-PCR, and ELISA. Secretory and gestational organoids recapitulated in vivo glandular epithelial phenotype (pan-cytokeratin, Muc-1, PAS, Laminin, and Ki67) and secretory and gestational features (\u03b1-tubulin, SOX9, SPP1, PAEP, LIF, and 17\u03b2HSD2 expression and SPP1 secretion). Adenomyosis organoids showed higher expression of TGF-\u03b22 and SMAD3 and increased gene expression of SPP1, PAEP, LIF, and 17\u03b2HSD2 compared with control organoids. Our results demonstrate that organoids derived from endometria of adenomyosis patients and differentiated to secretory and gestational phases recapitulate native endometrial-tissue-specific features and disease-specific traits. Adenomyosis-derived organoids are a promising in vitro preclinical model to study impaired implantation and pregnancy disorders in adenomyosis and enable personalized drug screening.<\/jats:p>","DOI":"10.3390\/jpm12020219","type":"journal-article","created":{"date-parts":[[2022,2,6]],"date-time":"2022-02-06T20:38:40Z","timestamp":1644179920000},"page":"219","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Establishment of Adenomyosis Organoids as a Preclinical Model to Study Infertility"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1850-5301","authenticated-orcid":false,"given":"Elena","family":"Ju\u00e1rez-Barber","sequence":"first","affiliation":[{"name":"Fundaci\u00f3n IVI, Instituto de Investigaci\u00f3n Sanitaria La Fe, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5202-8967","authenticated-orcid":false,"given":"Emilio","family":"Franc\u00e9s-Herrero","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n IVI, Instituto de Investigaci\u00f3n Sanitaria La Fe, 46026 Valencia, Spain"},{"name":"Departamento de Pediatr\u00eda, Obstetricia y Ginecolog\u00eda, Universidad de Valencia, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Corach\u00e1n","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n IVI, Instituto de Investigaci\u00f3n Sanitaria La Fe, 46026 Valencia, Spain"},{"name":"Departamento de Pediatr\u00eda, Obstetricia y Ginecolog\u00eda, Universidad de Valencia, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmina","family":"Vidal","sequence":"additional","affiliation":[{"name":"Departament of Gynecology, IVIRMA-Valencia, 46015 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Giles","sequence":"additional","affiliation":[{"name":"Departament of Gynecology, IVIRMA-Valencia, 46015 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pilar","family":"Alam\u00e1","sequence":"additional","affiliation":[{"name":"Departament of Gynecology, IVIRMA-Valencia, 46015 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amparo","family":"Faus","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n IVI, Instituto de Investigaci\u00f3n Sanitaria La Fe, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Pellicer","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n IVI, Instituto de Investigaci\u00f3n Sanitaria La Fe, 46026 Valencia, Spain"},{"name":"Departament of Gynecology, IVIRMA-Rome, 00197 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Cervell\u00f3","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n IVI, Instituto de Investigaci\u00f3n Sanitaria La Fe, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hortensia","family":"Ferrero","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n IVI, Instituto de Investigaci\u00f3n Sanitaria La Fe, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/j.fertnstert.2019.02.008","article-title":"Uterine polyps, adenomyosis, leiomyomas, and endometrial receptivity","volume":"111","author":"Munro","year":"2019","journal-title":"Fertil. 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