In humans, successful implantation requires a finely tuned synchrony between an appropriately developing embryo and the receptive endometrium, involving apposition, adhesion, and invasion. Therefore, this study was sought to establish a coculture cell model to investigate trophoblast-mediated blastocyst apposition and adhesion to endometrial epithelium events during embryo implantation. The direct contact and indirect noncontact coculture models were successfully established by using human BeWo trophoblasts and HEC-1A endometrial epithelial cells. Interestingly, a significant increase of ICAM-1 protein and mRNA expression was observed in both coculture systems when challenged with follicle-stimulating factor (FSH). In accordance with these observations, trophoblast-conditioned medium (CM) could also enhance epithelial ICAM-1 production, suggesting involvement of trophoblast-secreting factor(s) in crosstalk between two cells. Indeed, FSH stimulation enhanced TNF-α expression in the trophoblasts and epithelial ICAM-1 induction were abolished by a TNF-α blocking/ neutralizing antibody (TNF-α B/N Ab). Meanwhile, the intracellular calcium, PKA/CREB, and transcription/translation signaling pathways in epithelial cells participated in the ICAM-1 induction. Finally, the trophoblast cells were more susceptible to adhesion to CM-primed epithelial cell monolayer, where the adhesion could be abolished by TNF-α B/N Ab. Therefore, we present here novel findings that coculture of trophoblast with endometrial epithelial cells in the presence of FSH leads to an increase in epithelial ICAM-1 expression and trophoblast adhesion to epithelial monolayer through stimulating trophoblast’s TNF-α cytokine production. This study also addresses an important issue that a possible role of microenvironmental and exogenously-added FSH in enhancing blastocyst interaction with endometrium during embryo implantation of natural or in-vitro fertilization cycle.

Keywords:
Adhesion molecule, Follicle-stimulating factor, ICAM-1, Implantation, Trophoblast


J Reprod Immunol. 2022 Aug;152:103650. doi: 10.1016/j.jri.2022.103650. Epub 2022 Jun 6. PMID: 35696841.