Trophoblast-endometrial interaction in a 3D culture system as a model for early human implantation

• Applicant: Dr. Volker Uwe Buck
• Subject Area: Reproductive Medicine, Urology
• Term: from 2017 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 346386149

A basic requirement for human embryo implantation, which comprises penetration of endometrial epithelial cells (EEC) by trophoblast cells, is the appropriate preparation of the endometrium. Its cyclic differentiation leads to a short receptive period called window of implantation (WOI). About 30% of all pregnancies are lost during the early implantation phase. Insights in early mechanisms of human implantation may therefore improve the success rates of assisted reproductive technologies (ART).Our goal is to unravel basic mechanisms of early human implantation by using a newly established 3D cell culture confrontation system. Previously, in a study on human endometrial tissue we observed an altered distribution of adhering junctions along lateral membranes of glandular EEC during the WOI that indicates a change in EEC polarity. In the 3D cell culture confrontation system gland-like endometrial cell line spheroids with a junction distribution similar to EEC during the WOI were more strongly invaded by the extravillous trophoblast cell line AC-1M88 than spheroids that were derived from highly polarised endometrial cell lines.In the present project we will focus on the investigation of changes in epithelial junctional complexes and the associated cytoskeleton to elucidate mechanisms of trophoblast invasion. Using the established 2D and 3D culture systems as well as primary cells both spatial and temporal aspects of trophoblast-endometrial interaction will be analysed in detail by means of immunohistology and live cell imaging. By use of light sheet microscopy we expect a particularly high resolution of the invasive processes. A further aim is to analyse the influence of 17beta-estradiol and progesterone on endometrial epithelial receptivity and on the invasiveness of trophoblast cells.We expect that the results will provide new insights into the crucial mechanisms of human implantation and thus may help to improve the outcome of ART in the future.

• DFG Programme: Research Grants