Circulating Endometrial Cells: A New Source of Information on Endometriosis Dynamics

The focus of the presented work was to isolate and characterize circulating endometrial cells (CECs) enriched from peripheral blood (PB) of patients with diagnosed endometriosis. The molecular characteristics of CECs could be supportive for an understanding of endometriosis pathogenesis and treatment decisions in the future.

Blood samples (n = 423) were tested for CECs presence. Subsequently, gene expression analysis (GEA) was carried out for CECs. In parallel, CECs presence and characteristics were tested during menstrual cycle (MC) phases in 11 patients. CECs were enriched by size-based separation.

CECs were present in 78.4% of the tested blood samples. In line with the revised American Fertility Society (rAFS) classification, CECs presence was confirmed in all the acknowledged endometriosis stages: minimal, mild, moderate, and severe. Surprisingly, CECs negativity rate was also reported for severe disease in 21.1% of cases. The CECs captured during MC phases displayed different cytomorphology, including epithelial, stromal, and stem cell-like characteristics. The highest CECs numbers were detected in the mid-secretory phase of MC, which corresponds to uterine lining decidualization. CECs captured during mid-secretory periods expressed genes KRT18, NANOG, and VIM in higher amounts when compared to the proliferative phase of MC, where genes KRT19 and ESR1 were mostly elevated. GEA of the super-positive CECs samples (1000 CECs/8 mL PB) revealed high expression of genes KRT18, VIM, NANOG, and FLT1. The expression of these genes was also elevated in the endometriosis tissue samples and endometrioma.

The panel of the identified CEC genes could be tested in a prospective manner to confirm the role of CECs in endometriosis pathogenesis and diagnostics.