Evaluating the Implantation of Trophoblast Cells in an Artificial 3D Uterine Model

Abstract

During early embryo development, implantation is a critical point for delivery rates in mammals. Besides, the high rate of implantation failure remains a major problem in artificial reproductive fields. However, the mechanisms of implantation failure are still poorly understood. Implantation is complex process that involves a delicate coordination and a dialog between the blastocyst and the endometrium. Implantation process in human is different in some degree from that of mice and rats, and limiting the application of findings from animal studies to humans. On the other hand, in vivo research on implantation in humans is constrained by ethical issues. So, for implantation research, it is necessary to establish a in vitro model similar to that of humans. In here, PEG hydrogel and epithelial cell line Ishikawa (receptive endometrium), AN3CA (non-receptive endometrium) and human stromal cell line T-HESC were employed to mimic the endometrium, and choriocarcinoma cell lines (e.g. JAR JEG-3 and BeWo) for the blastocyst. The size of the spheroids increased with increasing culture time, and the cell viability was over 90%. The inner structure of the spheroids was full of cells, and Differentiated multinuclear cell structures were found at spheroid cultured for 72 h. In addition, different attachment and invasion rates were shown in response to epithelial cell monolayers of different properties. Through this, it can be seen that spheroids can grow and differentiate and have an appropriate reactivity to epithelial cells. Based on this, a 3D culture model was constructed. Put together, it is suggested that this configured model could be useful to mimic the maternal-embryo microenvironment and dissolve the various pathophysiological problems in human implantation.