Establishment of Rat Endometriosis Model by Autologous Endometrial Transplantation and Proof-of-Concept Pharmacological Validation with Elagolix.

Endometriosis (EM) is a common chronic gynecological disorder in women of reproductive age, yet its pathogenesis remains unclear, and current therapeutic options are limited by significant side effects. Endometriosis itself increases the risk of premature ovarian failure. Long-term lack of standardized treatment may accelerate the decline of ovarian function and prematurely trigger the aging process of the reproductive system. Reliable animal models are therefore essential for investigating disease mechanisms and evaluating novel treatments. This study presents a detailed protocol for establishing an endometriosis model in Sprague‑Dawley (SD) rats via autologous endometrial transplantation, and evaluates the therapeutic efficacy of the FDA‑approved gonadotropin‑releasing hormone (GnRH) antagonist Elagolix. The method involved excising uterine tissue, isolating endometrial fragments, and suturing them onto the peritoneal wall. At 21 days post‑surgery, ectopic lesions with typical cystic morphology had successfully formed in 18 out of 20 rats (90% success rate). Following model validation, Elagolix administration (100 mg/kg daily, oral gavage for 4 weeks) significantly reduced final lesion volume compared with the model group (inhibition rate: 86.7%), decreased serum levels of follicle‑stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2), and suppressed peritoneal cytokine levels, including tumor necrosis factor‑α (TNF‑α), vascular endothelial growth factor (VEGF), and interleukin‑6 (IL‑6). Histopathological examination revealed glandular atrophy, reduced epithelial proliferation, and diminished inflammatory infiltration in Elagolix‑treated lesions. The model demonstrated several advantages, including operational simplicity, high stability, and avoidance of immune rejection. The pharmacological response to GnRH antagonism in this model demonstrated biological activity consistent with the known mechanism of Elagolix, although pain-related and behavioral outcomes were not evaluated. Collectively, this model provides a standardized and reliable platform for mechanistic studies and preclinical drug efficacy assessment in endometriosis.