Embryo-derived human chorionic gonadotropin promotes human decidualization through activating epithelial prostaglandin F2α secretion

Decidualization of endometrial stromal cells is important for pregnancy in rodents and humans. Dysfunction of decidualization can lead to implantation failure and recurrent miscarriage. Although the amount of PGF2α in uterine fluid increases during embryo implantation, what stimulates the production of PGF2α in the uterus and whether PGF2α is involved in embryo implantation and decidualization are still unknown. In our study, human chorionic gonadotropin (hCG), an embryo-derived protein, stimulates human endometrial epithelial cells to increase the levels of PGF2α synthesis-related enzymes (cPLA2, COX-1, COX-2, and AKR1C3) and to secrete PGF2α. Epithelial PGF2α induces EREG and HB-EGF secretion by activating ADAM17. The level of IGFBP1, a marker of human in vitro decidualization, is significantly increased by EREG or HB-EGF. PGF2α is also able to increase the IGFBP1 level in humans during in vitro decidualization. Our results indicate that hCG stimulates uterine epithelial PGF2α production to induce in vitro decidualization through EREG and HB-EGF.