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Current hormonal and surgical treatments are often limited by side effects and high recurrence rates. In search of more effective and less invasive alternatives, we analyzed a single-cell RNA sequencing dataset of menstrual effluents from patients (GSE203191) and identified a significant upregulation of heat shock protein 90 (HSP90), suggesting its pathogenic involvement. Using primary endometrial stromal cells (ESCs) isolated from human ovarian endometrioma and a murine endometriosis model, we evaluated the therapeutic potential of HSP90 inhibition with 17-allylamino-17-demethoxygeldanamycin (17-AAG). In vitro, 17-AAG (10\u2009nM\u201310\u2009\u03bcM) reduced ESC viability and proliferation in a dose-dependent manner while increasing caspase-3 activity. In vivo, 17-AAG (30\u2009\u03bcg\/g) significantly attenuated ectopic lesion growth without impairing systemic parameters such as body weight, anti-M\u00fcllerian hormone, or estrogen levels. Proteomic profiling revealed disruption of HSP90 client networks, including downregulation of importin 4 and tubulin gamma complex protein 3, and upregulation of DnaJ heat shock protein family member B1, glutamate-ammonia ligase, and sequestosome 1. These findings highlight HSP90 as a promising non-hormonal therapeutic target in endometriosis, offering mechanistic insights and translational potential for more targeted, well-tolerated treatment strategies.<\/jats:p>","DOI":"10.1093\/reprod\/xaaf002","type":"journal-article","created":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T09:01:56Z","timestamp":1768467716000},"source":"Crossref","is-referenced-by-count":1,"title":["Targeting HSP90 as a therapeutic approach for endometriosis: insights from proteomic analysis"],"prefix":"10.1093","volume":"171","author":[{"given":"Jiayu","family":"Lin","sequence":"first","affiliation":[{"name":"Reproductive Medicine Center, The Sixth Affiliated Hospital, Sun Yat-sen University , Guangzhou, Guangdong, 510080,","place":["China"]},{"name":"Department of Obstetrics and Gynaecology, Li Ka Shing Faculty of Medicine, The University of Hong Kong , Hong Kong S.A.R, 999077,","place":["China"]},{"name":"Shenzhen Key Laboratory of Fertility Regulation, Reproductive Medicine Center, the University of Hong Kong-Shenzhen Hospital , Shenzhen, Guangdong, 518053,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weie","family":"Zhao","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center, The Sixth Affiliated Hospital, Sun Yat-sen University , Guangzhou, Guangdong, 510080,","place":["China"]},{"name":"Guangdong Engineering Technology Research Center of Fertility Preservation , Guangzhou, Guangdong, 510799,","place":["China"]},{"name":"Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University , Guangzhou, Guangdong, 510080,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manchao","family":"Li","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center, The Sixth Affiliated Hospital, Sun Yat-sen University , Guangzhou, Guangdong, 510080,","place":["China"]},{"name":"Guangdong Engineering Technology 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