Identification of Estrogen Receptor Regulates Stemness Properties of Endometrial Stem Cells and Its Clinical Significance in Endometriosis.

Endometriosis is the growth of endometrial tissues eutopically and/or ectopically. This disease affects nearly 10% of reproductive aged women with infertility. However, mechanism involved in endometriosis initiation still remains largely unknown. Stem cells in endometrial basalis layer have been hypothesized to mediate endometrium regeneration and endometriosis initiation. In clinic, estrogen is tightly associated with endometriosis. In this aspect, we hypothesized the role of estrogen in stemness gene expression and epithelial-mesenchymal transition (EMT) for endometriosis initiation. To test this hypothesis, endometrium tissues of normal endometrium , myoma, hyperplasia adenomyosis, and chocolate cyst were collected for stemness-related gene and CA125 analysis. Real-time PCR analysis showed high OCT-4 and NANOG expression and CA125 level in endometriosis tissues (adenomyosis and chocolate cyst). Immunohistochemical staining showed the OCT-4 protein expression was localized in luminal epithelial cells of human endometriosis tissues. Further experiments using a serum-free culture system to generate mouse epithelial-like endometrium stem cells (mEESCs) which expressed alkaline phosphatase activity, stem cell markers (such as Oct-4, SSEA-1, CD49f, CD63, and CD34), and IGF-1/IGF-1R (stemness regulatory signaling). In our study project not only in clinical medicine, but also provide a potential target therapy for drug development, while the stem cells into cancer stem cells contribute to basic research.