Investigating the Role of the Peritoneal Fluid in Endometriosis Lesion Establishment and Growth

Document Type

Article

Publication Date

2026

JAX Location

JGM

Abstract

Endometriosis is a chronic inflammatory disease in which endometrial-like tissue, known as lesions, grows outside the uterus in the peritoneal cavity, often causing heavy menstrual bleeding, severe pelvic pain, bladder and bowel symptoms, and reduced fertility. The role of the  peritoneal fluid (PF) surrounding these lesions in disease development remains poorly understood. To address this, this project grew patient-derived endometriosis and control cells exposed to PF supernatant to investigate the fluid’s effect on two of the main cell types found in endometriosis lesions: epithelial cells and uterine-like fibroblasts. Both cell types were grown in their optimal media alongside patient PF and PBS and imaged every 6 hours via live-imaging. We compared growth rates across multiple control and endometriosis patient cell lines and performed qPCR analysis on 12 epithelial gene markers to characterize the epithelial cells grown in PF compared to optimal media. We discovered that exposure to PF caused significant downregulation of genes associated with cellular proliferation, MKI67, and upregulation of secretory glandular genes, WNT7A and PAX8, revealing that the PF selects for differentiated epithelial cells and reinforces a glandular identity. Control and endometriosis lines exhibited similar changes in gene expression, suggesting phenotypic changes are driven by PF factors instead of innate differences in epithelial cells. Fibroblast cells in PF supernatant quickly proliferated when exposed to the peritoneal fluid, as compared to their typical fibroblast media, and created a web-like formation. These findings indicate that components within the PF supernatant may be a key driver of endometriosis lesion development.

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