17β-estradiol promotes bone marrow mesenchymal stem cell migration mediated by chemokine upregulation.

Bone marrow-derived cells engraft to the uterine endometrium and contribute to endometriosis. This study sought to further confirm that estrogen can promote the migration of bone marrow mesenchymal stem cells (BMSCs) and to investigate the function of estrogen on the secretion of chemokines during BMSC migration. BMSCs were treated with or without 17 beta-estradiol, cultured with or without endometrial stromal cells (ESCs), or pretreated with or without AMD 3100 (an antagonist of the SDF-1 alpha receptor) before co-culture. A migration assay was used to investigate the changes in the migration of BMSCs. The secretion of chemokines in the co-culture medium was detected by chemokine analysis, and the mRNA expression of SDF-1 alpha in cells was tested using quantitative real-time PCR. The results revealed that the migration of BMSCs was promoted by ESC, and the migration ability of BMSCs was enhanced after treatment with 17 beta-estradiol (p < 0.05). Through chemokine analysis, we further showed that 17 beta-estradiol promoted the secretion of chemokines especially for SDF-1 alpha (p < 0.05). Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that these chemokines were mainly linked to the cytokine signaling pathway and interaction with cytokines receptors. Furthermore, the expression of SDF-1 alpha mRNA was significantly increased in the 17 beta-estradiol treatment group (p < 0.001), and the migration of BMSCs was blocked by the use of our SDF-1 alpha antagonist (p < 0.01). Our results indicate that 17 beta-estradiol could promote the chemotaxis and migration of BMSCs by up-regulating the secretion of chemokines, especially SDF-1 alpha. Our study provides additional evidence to support and supplement the stem cell theory of endometriosis. (C) 2020 Elsevier Inc. All rights reserved.