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To identify an optimal syngeneic model exhibiting robust fibrosis and inflammation, we evaluated three inbred mouse strains: C57BL\/6J (<jats:italic>n<\/jats:italic> = 27), BALB\/c (<jats:italic>n<\/jats:italic> = 24), and Swiss albino (<jats:italic>n<\/jats:italic> = 27). Uterine fragments from donor mice were intraperitoneally transplanted into recipient mice (1 donor: 2 recipients) using an established protocol with minor modifications. All ENDO-induced mice displayed reduced burrowing and exploratory behaviors, alongside increased mechanical hyperalgesia, indicative of ENDO-associated discomfort. Peritoneal fluid analysis revealed a pro-inflammatory environment with a tendency towards an M2 macrophage-dominant profile across all strains. Histological examination confirmed endometriotic lesions with proliferating epithelium (Ki-67+), neovascularization (CD31+), and macrophage infiltration (F4\/80+). Notably, C57BL\/6J mice exhibited the highest ENDO incidence and a significantly pronounced fibrotic response, evidenced by increased stromal collagen deposition and elevated Col1A1, cytokeratin, \u03b1-Smooth Muscle Actin (\u03b1-SMA), and Nestin expression. Molecular analysis in C57BL\/6J mice further supported epithelial-mesenchymal transition (EMT)-driven fibrosis, with decreased E-cadherin and increased N-cadherin and S100A4 mRNA levels, corroborated by corresponding protein changes (cytokeratin, vimentin, snail). Our findings establish the C57BL\/6J strain as the most suitable syngeneic model for ENDO, consistently recapitulating the inflammatory and fibrotic pathophysiology observed in human disease, particularly its fibrotic component.<\/jats:p>","DOI":"10.1038\/s41598-025-13900-9","type":"journal-article","created":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T07:34:07Z","timestamp":1754638447000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["C57BL\/6J mice best recapitulate fibrosis and inflammatory pathophysiology in syngeneic mouse model of endometriosis"],"prefix":"10.1038","volume":"15","author":[{"given":"Megha","family":"Anchan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atharvaraj","family":"Hande","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samruddhi","family":"Deshpande","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richa","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guruprasad","family":"Kalthur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jahnavy Madhukar","family":"Joshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ratul","family":"Datta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swar","family":"Shah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kriti","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiral","family":"Pandya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul","family":"Dutta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,8]]},"reference":[{"key":"13900_CR1","doi-asserted-by":"publisher","first-page":"102454","DOI":"10.1016\/j.bpobgyn.2023.102454","volume":"92","author":"R Leone","year":"2024","unstructured":"Leone, R. et al. 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