{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:38:09Z","timestamp":1791221889145,"version":"4.1.0"},"reference-count":57,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T00:00:00Z","timestamp":1745798400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Russian Science Foundation","award":["#24-74-10002"],"award-info":[{"award-number":["#24-74-10002"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cellular senescence has emerged as a key mediator in organ-specific fibrosis. Here, we have established the role of endometrial stromal senescence in the progression of endometrial fibrosis, termed intrauterine adhesions (IUA). IUA have significant negative effects on women\u2019s reproductive health and are associated with infertility. We have generated original gene signatures to identify endometrial stromal senescence in single-cell and bulk RNA-sequencing data. By applying generated gene signatures, we revealed an increased level of stromal senescence during the proliferative phase in the endometrium of patients with IUA. Further comparative analysis of cell\u2013cell communications demonstrated that senescent stromal cells in the IUA endometrium create an immunosuppressive and profibrotic microenvironment through an elevated expression of LGALS9. Endometrial stromal senescence persists during the window of implantation and correlates with impaired embryo receptivity of the IUA endometrium. Therefore, stromal senescence can be regarded as a primary cause of an unresponsive endometrium with decreased receptivity and thickness in IUA patients. A LGALS9 immunotherapy protocol, specifically designed to neutralize LGALS9 immunosuppressive activity of senescent cells, may offer a promising opportunity to restore effective immune clearance of these cells within the IUA stroma. Consequently, an LGALS9-based strategy could emerge as a novel therapeutic avenue in the treatment of IUA.<\/jats:p>","DOI":"10.3390\/ijms26094183","type":"journal-article","created":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T05:17:12Z","timestamp":1745903832000},"page":"4183","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Endometrial Stromal Senescence Mediates the Progression of Intrauterine Adhesions"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2451-2943","authenticated-orcid":false,"given":"Pavel I.","family":"Deryabin","sequence":"first","affiliation":[{"name":"Mechanisms of Cellular Senescence Laboratory, Institute of Cytology of the Russian Academy of Sciences, Tikhoretsky Ave. 4, Saint-Petersburg 194064, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1675-7588","authenticated-orcid":false,"given":"Aleksandra V.","family":"Borodkina","sequence":"additional","affiliation":[{"name":"Mechanisms of Cellular Senescence Laboratory, Institute of Cytology of the Russian Academy of Sciences, Tikhoretsky Ave. 4, Saint-Petersburg 194064, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s00281-024-01030-9","article-title":"Mechanistic insights into intrauterine adhesions","volume":"47","author":"Zhao","year":"2024","journal-title":"Semin. 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