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The Biological Characteristics of Eutopic and Ectopic Endometrial Progenitor Cells in Endometriosis. 2023

Qingxia Zhang, and Jing Liang, and Dongkui Xu, and Ting Gao, and Jinku Zhang, and Haiyan Liang, and Wenhui Wang, and Bin Ling, and Dingqing Feng
Department of Obstetrics and Gynecology, China-Japan Friendship Hospital, Beijing, 100029, China.

OBJECTIVE The aim of this study was to identify the biological characteristics and potential roles of endometrial progenitor cells in the pathogenesis of endometriosis. BACKGROUND It is generally believed that progenitor cells in human endometrium are responsible for rapid endometrial regeneration. However, the biological characteristics and potential roles of the paired eutopic and ectopic endometrial progenitor cells in endometriosis remain unclear. OBJECTIVE This study intends to isolate the epithelial progenitor (EP) cells and endometrial mesenchymal stem cells (eMSCs) from the eutopic and ectopic endometria from endometriosis patients, further to reveal their features and functions respectively. METHODS The distributions of EP cells and eMSCs and the expression of steroid hormone receptors in the endometrium and endometriotic tissues were assessed by immunohistochemistry. EP cells and eMSCs were sorted from paired eutopic and ectopic endometria with epithelial cell adhesion molecule (EpCAM) magnetic beads. The clonogenicity, cell viability after being treated with estradiol and progesterone, and cell markers expression were evaluated with colony forming on Matrigel, CCK-8 and immunofluorescence staining, respectively. The differentially expressed genes (DEGs) were further identified with RNA sequencing. RESULTS SSEA-1- and PDGFRβ-positive cells were distributed in the epithelial and stromal layers. The ERβ staining was much more intense in endometriotic tissues, but PR expression was almost absent. The ectopic EP cells exhibit strong clonogenicity and ERβ expression but weak PR expression, leading to progesterone resistance. There are 12604 and 13242 DEGs revealed by RNA sequencing between eutopic and ectopic EP cells or eMSCs. GO and KEGG analyses revealed that the functions and pathways of DEGs enriched in cellular energy metabolism and regulation of the immune response, respectively. Additionally, ERβ targets were mainly enriched in ectopic EP cells. CONCLUSIONS Both EP cells and eMSCs may engage in ectopic lesion formation in endometriosis by modifying the metabolic mode and immune tolerance. These data not only help to understand the molecular mechanism of endometriosis but also could potentially contribute to the discovery of therapeutic targets for endometriosis.

UI MeSH Term Description Entries
D004715 Endometriosis A condition in which functional endometrial tissue is present outside the UTERUS. It is often confined to the PELVIS involving the OVARY, the ligaments, cul-de-sac, and the uterovesical peritoneum. Endometrioma,Endometriomas,Endometrioses
D004717 Endometrium The mucous membrane lining of the uterine cavity that is hormonally responsive during the MENSTRUAL CYCLE and PREGNANCY. The endometrium undergoes cyclic changes that characterize MENSTRUATION. After successful FERTILIZATION, it serves to sustain the developing embryo. Endometria
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013234 Stem Cells Relatively undifferentiated cells that retain the ability to divide and proliferate throughout postnatal life to provide progenitor cells that can differentiate into specialized cells. Colony-Forming Units,Mother Cells,Progenitor Cells,Colony-Forming Unit,Cell, Mother,Cell, Progenitor,Cell, Stem,Cells, Mother,Cells, Progenitor,Cells, Stem,Colony Forming Unit,Colony Forming Units,Mother Cell,Progenitor Cell,Stem Cell
D014591 Uterine Diseases Pathological processes involving any part of the UTERUS. Endometrial Diseases,Disease, Endometrial,Disease, Uterine,Diseases, Endometrial,Diseases, Uterine,Endometrial Disease,Uterine Disease
D047629 Estrogen Receptor beta One of the ESTROGEN RECEPTORS that has greater affinity for ISOFLAVONES than ESTROGEN RECEPTOR ALPHA does. There is great sequence homology with ER alpha in the DNA-binding domain but not in the ligand binding and hinge domains. ERbeta,ERbetacx,Estrogen Receptor 2,Estrogen Receptors beta,Receptor beta, Estrogen

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