{"paper_id":"e6b1f7bb-bfc9-46e6-b194-0d2db9715448","body_text":"Comparison of Surgically-Induced Endometriosis Models in Rats and the Role of VEGF: A Novel VEGF-Enhanced Rat Model of Endometriosis\nAbstract\nPurpose: Endometriosis is an inflammatory disease characterized by the presence of endometrial tissue outside the uterine cavity. Animal models that reflect the characteristics of human disease have been critical for research in this field. We sought to develop and validate a novel rat model for endometriosis, incorporating vascular endothelial growth factor (VEGF) to enhance disease formation and explore disease-related characteristics.\nMaterials and Methods: Forty adult female non-mated Wistar albino rats were divided into four groups: control, Vernon-Wilson method, peritoneal endometrial tissue injection, and peritoneal endometrial tissue injection with VEGF pre-treatment. All rats underwent oophorectomy to stabilize estrogen levels, followed by oral administration of 17β-estradiol for 21 days. Histopathological and immunohistochemical evaluations were performed to assessendometriosis severity, stromal development, CD10 positivity, estrogen receptor (ER) staining, VEGF staining, and inflammatory activity.\nResults: All three models generated significant differences compared to controls. The injection + VEGFgroup exhibited extensive endometriosis development, with higher epithelial density, stromal presence, andVEGF staining intensity compared to other groups, and similar overall endometriosis score to the Vernon-Wilson model. ER positivity was most pronounced in the Vernon-Wilson group, while stromal density and angiogenesis were higher in VEGF recipients.\nConclusion: This study introduces a VEGF-enhanced rat model as an efficient and reproducible tool for studying endometriosis. This model emulates pathological features associated with endometriosis, including angiogenesis, immune response, and inflammation, but does not appear to generate ER positivity at the level of the Vernon-Wilson model. Despite this limitation, we believe this simple and efficient model can be crucial for researchers studying endometriosis.\nKeywords\nSupporting Institution\nProject Number\nEthical Statement\nReferences\n- Sanamiri K, Mahdian S, Moini A, Shahhoseini M. Non-hormonal therapy for endometriosis based on angiogenesis oxidative stress and inflammation. Int J Fertil Steril. 2024;18(4): 305–313. doi:10.22074/ijfs.2024.2012554.1547\n- Maenhoudt N, De Moor A, Vankelecom H. Modeling endometrium biology and disease. J Pers Med. 2022;12(7):1048. doi:10.3390/jpm12071048\n- Zheng P, Jia S, Guo D, et al. Central sensitization-related changes in brain function activity in a rat endometriosis-associated pain model. J Pain Res. 2020;13:95-107. doi:10.2147/JPR.S232313\n- Grümmer R. Animal models in endometriosis research. Hum Reprod Update. 2006;12(5):641-649. doi:10.1093/humupd/dml026\n- Tan Z, Hung SW, Zheng X, Wang CC, Chung JPW, Zhang T. What we have learned from animal models to understand the etiology and pathology of endometrioma-related infertility. Biomedicines. 2022;10(7):1483. doi:10.3390/biomedicines10071483\n- Osteen KG, Yeaman GR, Bruner-Tran KL. Matrix metalloproteinases and endometriosis. Semin Reprod Med. 2003;21(2):155-164. doi:10.1055/s-2003-41322\n- Ozer H, Boztosun A, Açmaz G, Atılgan R, Akkar OB, Kosar MI. The efficacy of Bevacizumab, Sorafenib, and Retinoic Acid on rat endometriosis model. Reprod Sci. 2013;20(1):26-32. doi:10.1177/1933719112452941\n- McLaren J, Prentice A, Charnock-Jones DS, Smith SK. Vascular endothelial growth factor (VEGF) concentrations are elevated in peritoneal fluid of women with endometriosis. Hum Reprod. 1996;11(1):220-223. doi:10.1093/oxfordjournals.humrep.a019023\nDetails\nPrimary Language\nEnglish\nSubjects\nClinical Sciences (Other)\nJournal Section\nResearch Article\nAuthors\nSelin Mutlu\n*\n0000-0003-3200-5079\nTürkiye\nÇağlar Yıldız\n0000-0003-3150-3340\nTürkiye\nBegüm Kurt\nThis is me\n0000-0002-7166-3130\nTürkiye\nNeşe Yeldir\n0000-0002-3812-6245\nTürkiye\nEren Cemal Mutlu\n0000-0002-6072-8509\nTürkiye\nPublication Date\nAugust 31, 2026\nSubmission Date\nOctober 6, 2025\nAcceptance Date\nFebruary 28, 2026\nPublished in Issue\nYear 2026 Volume: 10 Number: 2","source_license":"CC0","license_restricted":false}