C57BL/6J mice best recapitulate fibrosis and inflammatory pathophysiology in syngeneic mouse model of endometriosis.

Endometriosis (ENDO), a chronic inflammatory disease affecting approximately 190 million women globally, is characterized by fibrosis, a feature often challenging to replicate in murine models. To identify an optimal syngeneic model exhibiting robust fibrosis and inflammation, we evaluated three inbred mouse strains: C57BL/6J (n = 27), BALB/c (n = 24), and Swiss albino (n = 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, α-Smooth Muscle Actin (α-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.