Mechanism of HCG regulating epithelial-mesenchymal transition progression in endometrial cells through the FoxO1/miR223-5p/Wnt5a pathway

Research question: Does human chorionic gonadotrophin (HCG) influence endometrial receptivity and epithelial-mesenchymal transition (EMT) via the FoxO1/miR223-5p/Wnt5a pathway? Design: This study aimed to establish the co -culture system of human embryonic trophoblast cell line (HTR-8-Svneo) cells and human endometrial epithelial cell line (HEEC) cells. The expression of Wnt5a protein and EMT -related proteins in HTR-8-Svneo and HEEC cells treated in a gradient -dependent manner using HCG and exosome inhibitor GW4869 were detected in the coculture system. Results: In the HTR-8-Svneo/HEEC co -culture system, miR223-5p in HEEC cells increased significantly with induction of HTR-8Svneo cells by 100 IU/ml HCG for 48 h (P = 0.046), and Wnt5a protein decreased significantly in HEEC cells (P = 0.021). Pretreatment of HTR-8-Svneo cells with GW4869, and knockdown of FoxO1 in HTR-8-Svneo cells, significantly inhibited the above effects of HCG on miR223-5p and Wnt5a expression in HEEC cells in the HTR-8-Svneo/HEEC co -culture system. HTR-8Svneo cells induced with 100 IU/ml HCG for 48 h significantly enhanced the logarithmic phase proliferation activity of HEEC cells in the co -culture system (P < 0.001), while knockdown of FoxO1 in HTR-8-Svneo cells and inhibition of miR223-5p in HEEC cells suppressed proliferation of HEEC cells in the HTR-8-Svneo/HEEC co -culture system (P < 0.001). Conclusions: HCG exposure induces HTR-8-Svneo cells to up -regulate miR223-5p expression, which enters HEEC cells in the co -culture system through the exosomal pathway, and inhibits Wnt5a expression and the progress of EMT.