Endometrial Stromal Cells from Endometriosis Patients Reflect Lesion-Type-Specific Heterogeneity

Endometriosis, a disease affecting about one out of ten women, is characterized by the growth of endometrial-like tissue outside the uterine cavity. There is significant disease heterogeneity, but the pathophysiological mechanisms underlying differences in clinical presentation are poorly understood. Here, we investigated endometrial stromal cells (ESCs) from different types of endometrial lesions (endometrioma, superficial, and deep endometrial lesions), which revealed distinct differences in proliferation, migration, and contractility among different lesion types and when compared to ESC from normal (eutopic) endometrium. In particular, ESCs from endometriotic lesions showed reduced proliferation but increased migratory capacity, an effect most pronounced in endometrioma ESCs but also evident in ESCs from superficial and deep lesions. ESCs from superficial and deep lesions-but not those from endometrioma-showed increased contractility, a feature involved in tissue scarring and pain perception. Transcriptomics and proteomics revealed changes in genes and proteins involved in cell division, proliferation, extracellular matrix organization, and migration in endometriosis vs. healthy ESCs. Overall, our results demonstrate that stromal cells from different endometriotic lesions show distinct in vitro phenotypes that might explain differences in clinical presentation. Further, these cells represent an excellent in vitro model for studying patho-mechanisms involved in endometriosis heterogeneity.