Migration of Cells from Experimental Endometriosis to the Uterine Endometrium

Endometriosis is the estrogen-dependent growth of endometrial tissue outside the uterus. Endometriosis has an effect on the eutopic endometrium; however, the nature of the cellular or molecular signal from the lesion to the uterus is unknown. Here we demonstrate that cells migrate from endometriosis to eutopic endometrium. Experimental endometriosis was established by transplanting endometrial tissue from green fluorescent protein (GFP) mice to the peritoneal cavity of DS-Red mice. Immunofluorescence (IF) identified cells from the ectopic lesions in the uterus. The eutopic endometrial cells were sorted by fluorescence activated cell sorting, and the GFP(+)/DS-Red(-) population was characterized using microarray analysis. The results of cell sorting as well as the array results were confirmed by quantitative PCR and IF. GFP(+)/DS-red(-)/Cd45(-) cells were identified in the eutopic endometrium of mice with experimental endometriois (similar to 1.8%) and not in controls. Global gene expression profiling of these cells showed absence of leukocyte and increased expression of pan-epithelial markers in the uterine GFP(+) cells. Moreover, GFP(+) cells showed up-regulation of Wnt7A expression and 17 other genes associated with the Wingless pathway. Several genes that are associated with epithelial-to-mesenchymal transition were also highly differentially expressed in GFP(+) cells. IF confirmed the presence of the GFP(+)/CD45(-)/Wnt7a(+)/cytokeritin(+) cells in the endometrium of endometriotic animals, and not in controls. Cells from endometriotic lesions are capable of migrating to the eutopic endometrium. The ectopic expression of Wnt7A suggests a possible mechanism by which ectopic lesions affect the eutopic endometrium and interfere with embryo implantation and fertility. (Endocrinology 153: 5566-5574, 2012)