{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,15]],"date-time":"2026-03-15T21:56:19Z","timestamp":1773611779092,"version":"3.50.1"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:00:00Z","timestamp":1771459200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFC2705403"],"award-info":[{"award-number":["2023YFC2705403"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Transmembrane protein TMEM119 has been implicated in tumor progression (e.g., ovarian cancer), but its role and underlying mechanism in ovarian endometriosis (EM) remain elusive. Thus, this study aimed to investigate the expression pattern and functional role of TMEM119 in ovarian EM. To this end, TMEM119 expression was first analyzed using the GSE141549 dataset, and further detected in ovarian EM tissues and ovarian ectopic endometrial stromal cells (ESCs). After TMEM119 overexpression in ectopic ESCs, gene ontology\/Kyoto Encyclopedia of Genes and Genomes enrichment analyses of differentially expressed genes (DEGs) were conducted. For ectopic ESCs with TMEM119 knockdown or overexpression [divided into four groups: negative control (NC)-short hairpin (sh) RNA, TMEM119-shRNA, NC-overexpression (OE), and TMEM119-OE], we detected cell cycle distribution, positive rates of p16, p21, and p53, senescence-associated \u03b2-galactosidase positivity, cell proliferation, and the expression of p53 and mitogen-activated protein kinase (MAPK) pathway-related proteins. Molecular docking was performed to evaluate the binding affinity between TMEM119 and therapeutic drugs for ovarian EM. Results showed that TMEM119 was significantly upregulated in ovarian EM tissues and ovarian ectopic ESCs. TMEM119 knockdown induced senescence in ectopic ESCs\u2014evidenced by increased positive rates of p16 and p21, G0\/G1 phase arrest, and accumulated senescence-associated \u03b2-galactosidase positivity\u2014accompanied by decreased cell proliferation and MAPK phosphorylation. In contrast, TMEM119 overexpression exerted the opposite effects. However, the change in p53 protein expression was not obvious. Molecular docking showed that TMEM119 exhibited strong binding affinity for danazol, drospirenone, and sufugolix. Collectively, TMEM119 is significantly upregulated in ovarian EM, where it blocks ectopic ESC senescence via MAPK signaling and consequently accelerates lesion expansion. Inducing cellular senescence may therefore constitute a tractable therapeutic avenue for ovarian EM.<\/jats:p>","DOI":"10.1093\/reprod\/xaag021","type":"journal-article","created":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T12:41:33Z","timestamp":1770986493000},"source":"Crossref","is-referenced-by-count":0,"title":["TMEM119 links to ovarian endometriosis progression via MAPK-mediated suppression of ectopic endometrial stromal cell senescence"],"prefix":"10.1093","volume":"171","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-2223-5359","authenticated-orcid":false,"given":"Liansuo","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Jinshan Hospital, Fudan University , Shanghai,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7722-2145","authenticated-orcid":false,"given":"Zouyu","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Jinshan Hospital, Fudan University , Shanghai,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1126-5939","authenticated-orcid":false,"given":"Wei","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Jinshan Hospital, Fudan University , Shanghai,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3317-3883","authenticated-orcid":false,"given":"Yanchun","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Jinshan Hospital, Fudan University , Shanghai,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9276-0722","authenticated-orcid":false,"given":"Mingqing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Reproductive Immunology, The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai,","place":["China"]},{"name":"The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai Key Laboratory of Embryo Original Diseases, , Shanghai,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9023-8400","authenticated-orcid":false,"given":"Songping","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Jinshan Hospital, Fudan University , Shanghai,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2026,2,19]]},"reference":[{"key":"2026031517312245900_xaag021-B1","doi-asserted-by":"publisher","first-page":"953055","DOI":"10.3389\/fonc.2022.953055","article-title":"LncRNA HOTAIR regulates cell invasion and migration in endometriosis through miR-519b-3p\/PRRG4 pathway","volume":"12","author":"Bao","year":"2022","journal-title":"Frontiers in Oncology"},{"key":"2026031517312245900_xaag021-B2","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1001\/jama.2024.9210","article-title":"Endometriosis typology and ovarian cancer risk","volume":"332","author":"Barnard","year":"2024","journal-title":"JAMA"},{"key":"2026031517312245900_xaag021-B3","doi-asserted-by":"publisher","first-page":"103752","DOI":"10.1016\/j.autrev.2025.103752","article-title":"Endometriosis and autoimmunity","volume":"24","author":"Blanco","year":"2025","journal-title":"Autoimmunity Reviews"},{"key":"2026031517312245900_xaag021-B4","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.1152\/physrev.00020.2018","article-title":"Cellular senescence: aging, cancer, and injury","volume":"99","author":"Calcinotto","year":"2019","journal-title":"Physiological Reviews"},{"key":"2026031517312245900_xaag021-B5","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1146\/annurev-physiol-030212-183653","article-title":"Aging, cellular senescence, and cancer","volume":"75","author":"Campisi","year":"2013","journal-title":"Annual Review of Physiology"},{"key":"2026031517312245900_xaag021-B6","doi-asserted-by":"publisher","first-page":"e2100558118","DOI":"10.1073\/pnas.2100558118","article-title":"TMEM70 and TMEM242 help to assemble the rotor ring of human ATP synthase and interact with assembly factors for complex I","volume":"118","author":"Carroll","year":"2021","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"2026031517312245900_xaag021-B7","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1093\/biolre\/iox099","article-title":"Iron suppresses ovarian granulosa cell proliferation and arrests cell cycle through regulating p38 mitogen-activated protein kinase\/p53\/p21 pathway","volume":"97","author":"Chen","year":"2017","journal-title":"Biology of Reproduction"},{"key":"2026031517312245900_xaag021-B8","doi-asserted-by":"publisher","first-page":"1503477","DOI":"10.3389\/fcell.2025.1503477","article-title":"Roxadustat regulates the cell cycle and inhibits proliferation of mesangial cells via the hypoxia-inducible factor-1\u03b1\/P53\/P21 pathway","volume":"13","author":"Cheng","year":"2025","journal-title":"Frontiers in Cell and Developmental Biology"},{"key":"2026031517312245900_xaag021-B9","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1186\/s12958-024-01265-z","article-title":"Quercetin enhances decidualization through AKT-ERK-p53 signaling and supports a role for senescence in endometriosis","volume":"22","author":"Delenko","year":"2024","journal-title":"Reproductive Biology and Endocrinology: RB&E"},{"key":"2026031517312245900_xaag021-B10","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1038\/s41580-020-00314-w","article-title":"Cellular senescence in ageing: from mechanisms to therapeutic opportunities","volume":"22","author":"Di Micco","year":"2021","journal-title":"Nature Reviews. Molecular Cell Biology"},{"key":"2026031517312245900_xaag021-B11","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1186\/s10020-025-01130-8","article-title":"A novel mechanism of FTO modulating the progression of endometriosis through mediating the m6A methylation of GEF-H1 in a YTHDF1-dependent manner","volume":"31","author":"Ding","year":"2025","journal-title":"Molecular Medicine (Cambridge, Mass.)"},{"key":"2026031517312245900_xaag021-B12","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1016\/j.cell.2019.10.005","article-title":"Cellular senescence: Defining a path forward","volume":"179","author":"Gorgoulis","year":"2019","journal-title":"Cell"},{"key":"2026031517312245900_xaag021-B13","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1016\/j.molmed.2024.06.008","article-title":"Endometriosis: recent advances that could accelerate diagnosis and improve care","volume":"30","author":"Griffiths","year":"2024","journal-title":"Trends in Molecular Medicine"},{"key":"2026031517312245900_xaag021-B14","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1093\/humrep\/dey336","article-title":"Abnormally located SSEA1+\/SOX9+ endometrial epithelial cells with a basalis-like phenotype in the eutopic functionalis layer may play a role in the pathogenesis of endometriosis","volume":"34","author":"Hapangama","year":"2019","journal-title":"Human Reproduction (Oxford, England)"},{"key":"2026031517312245900_xaag021-B15","doi-asserted-by":"publisher","first-page":"1244740","DOI":"10.3389\/fonc.2023.1244740","article-title":"The transmembrane proteins (TMEM) and their role in cell proliferation, migration, invasion, and epithelial-mesenchymal transition in cancer","volume":"13","author":"Herrera-Quiterio","year":"2023","journal-title":"Frontiers in Oncology"},{"key":"2026031517312245900_xaag021-B16","doi-asserted-by":"publisher","first-page":"e070750","DOI":"10.1136\/bmj-2022-070750","article-title":"Pathophysiology, diagnosis, and management of endometriosis","volume":"379","author":"Horne","year":"2022","journal-title":"BMJ (Clinical Research ed.)"},{"key":"2026031517312245900_xaag021-B17","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1038\/s41419-025-07724-8","article-title":"USP14\/S100A11 axis promote colorectal cancer progression by inhibiting cell senescence","volume":"16","author":"Huang","year":"2025","journal-title":"Cell Death & Disease"},{"key":"2026031517312245900_xaag021-B18","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1093\/humupd\/dmaa045","article-title":"Endometriosis and cancer: a systematic review and meta-analysis","volume":"27","author":"Kvaskoff","year":"2021","journal-title":"Human Reproduction Update"},{"key":"2026031517312245900_xaag021-B19","doi-asserted-by":"publisher","first-page":"4150","DOI":"10.1016\/j.cell.2024.05.059","article-title":"Guidelines for minimal information on cellular senescence experimentation in vivo","volume":"187","author":"Ogrodnik","year":"2024","journal-title":"Cell"},{"key":"2026031517312245900_xaag021-B20","doi-asserted-by":"publisher","first-page":"1324429","DOI":"10.3389\/fendo.2023.1324429","article-title":"Chronic low-grade inflammation and ovarian dysfunction in women with polycystic ovarian syndrome, endometriosis, and aging","volume":"14","author":"Orisaka","year":"2023","journal-title":"Frontiers in Endocrinology"},{"key":"2026031517312245900_xaag021-B21","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1016\/S0002-9378(15)30003-X","article-title":"Peritoneal endometriosis due to the menstrual dissemination of endometrial tissue into the peritoneal cavity","volume":"14","author":"Sampson","year":"1927","journal-title":"American Journal of Obstetrics and Gynecology"},{"key":"2026031517312245900_xaag021-B22","doi-asserted-by":"publisher","first-page":"2807","DOI":"10.1016\/j.cell.2021.04.041","article-title":"Endometriosis: Etiology, pathobiology, and therapeutic prospects","volume":"184","author":"Saunders","year":"2021","journal-title":"Cell"},{"key":"2026031517312245900_xaag021-B23","doi-asserted-by":"publisher","first-page":"1345","DOI":"10.3389\/fphar.2018.01345","article-title":"TMEM proteins in cancer: A review","volume":"9","author":"Schmit","year":"2018","journal-title":"Frontiers in Pharmacology"},{"key":"2026031517312245900_xaag021-B24","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1038\/nrc3960","article-title":"Forging a signature of in vivo senescence","volume":"15","author":"Sharpless","year":"2015","journal-title":"Nature Reviews. Cancer"},{"key":"2026031517312245900_xaag021-B25","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1186\/s12967-021-02781-x","article-title":"TMEM119 facilitates ovarian cancer cell proliferation, invasion, and migration via the PDGFRB\/PI3K\/AKT signaling pathway","volume":"19","author":"Sun","year":"2021","journal-title":"Journal of Translational Medicine"},{"key":"2026031517312245900_xaag021-B26","doi-asserted-by":"publisher","first-page":"3491","DOI":"10.1038\/s41388-023-02853-w","article-title":"S1PR1 regulates ovarian cancer cell senescence through the PDK1-LATS1\/2-YAP path\u00adway","volume":"42","author":"Tao","year":"2023","journal-title":"Oncogene"},{"key":"2026031517312245900_xaag021-B27","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1016\/S0140-6736(21)00389-5","article-title":"Endometriosis is a chronic systemic disease: clinical challenges and novel innovations","volume":"397","author":"Taylor","year":"2021","journal-title":"Lancet (London, England)"},{"key":"2026031517312245900_xaag021-B28","doi-asserted-by":"publisher","first-page":"12302","DOI":"10.1038\/s41598-022-16629-x","article-title":"SIRT1 upregulation promotes epithelial-mesenchymal transition by inducing senescence escape in endometriosis","volume":"12","author":"Wang","year":"2022","journal-title":"Scientific Reports"},{"key":"2026031517312245900_xaag021-B29","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1186\/s12967-023-04209-0","article-title":"METTL3-mediated m6A modification of SIRT1 mRNA inhibits progression of endometriosis by cellular senescence enhancing","volume":"21","author":"Wang","year":"2023","journal-title":"Journal of Translational Medicine"},{"key":"2026031517312245900_xaag021-B30","doi-asserted-by":"publisher","first-page":"4856","DOI":"10.1080\/21655979.2021.1960464","article-title":"Transmembrane protein TMEM119 facilitates the stemness of breast cancer cells by activating Wnt\/\u03b2-catenin pathway","volume":"12","author":"Yang","year":"2021","journal-title":"Bioengineered"},{"key":"2026031517312245900_xaag021-B31","doi-asserted-by":"publisher","first-page":"e158450","DOI":"10.1172\/JCI158450","article-title":"Cellular senescence: A key therapeutic target in aging and diseases","volume":"132","author":"Zhang","year":"2022","journal-title":"The Journal of Clinical Investigation"},{"key":"2026031517312245900_xaag021-B32","doi-asserted-by":"publisher","first-page":"5835","DOI":"10.2147\/OTT.S164045","article-title":"TMEM119 promotes gastric cancer cell migration and invasion through STAT3 signaling pathway","volume":"11","author":"Zheng","year":"2018","journal-title":"OncoTargets and Therapy"},{"key":"2026031517312245900_xaag021-B33","doi-asserted-by":"publisher","first-page":"1244","DOI":"10.1056\/NEJMra1810764","article-title":"Endometriosis","volume":"382","author":"Zondervan","year":"2020","journal-title":"The New England Journal of Medicine"}],"container-title":["Reproduction"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/reproduction\/advance-article-pdf\/doi\/10.1093\/reprod\/xaag021\/66993703\/xaag021.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/reproduction\/article-pdf\/171\/3\/xaag021\/66993703\/xaag021.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/reproduction\/article-pdf\/171\/3\/xaag021\/66993703\/xaag021.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,15]],"date-time":"2026-03-15T21:31:28Z","timestamp":1773610288000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/reproduction\/article\/doi\/10.1093\/reprod\/xaag021\/8490778"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,19]]},"references-count":33,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3,15]]}},"URL":"https:\/\/doi.org\/10.1093\/reprod\/xaag021","relation":{},"ISSN":["1470-1626","1741-7899"],"issn-type":[{"value":"1470-1626","type":"print"},{"value":"1741-7899","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,3]]},"published":{"date-parts":[[2026,2,19]]},"article-number":"xaag021"}}