Abstract Endometriosis, a chronic inflammatory condition characterized by pain and infertility, remains a clinical challenge. 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（scRNA-seq） 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 nM–10 μM) reduced ESC viability and proliferation in a dose-dependent manner while increasing caspase-3 activity. In vivo, 17-AAG (30 μg/g) significantly attenuated ectopic lesion growth without impairing systemic parameters such as body weight, AMH, or estrogen levels. Proteomic profiling revealed disruption of HSP90 client networks, including downregulation of IPO4 and TUBGCP3, and upregulation of DNAJB1, GLUL and SQSTM1. 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.
Lin et al. (Thu,) studied this question.