Embryonic serine - proteases as important signals to initiate the embryo implantation

Infertility is a problem that affects 10% of the global population of reproductive age. In vitro Fertilization is currently the best to help infertile couples. Unfortunately, many couples who start a first IVF-cycle will not end with a live birth because of embryo implantation problems. However, the complex process of implantation has yet to be understood.

The overall goal is to achieve novel insights into the first steps of the implantation process and will focus on the role of calcium influx in epithelial cells. This may represent a key regulatory mechanism to initiate or regulate downstream processes of the embryo implantation process, such as decidualization and blastocyst adhesion. Unpublished results showed robust influxes in Ca2+ concentrations in endometrial epithelial cells after stimulation by the serine-protease trypsin secreted by the blastocyst. Moreover, we identified the functional expression of a mechanosensitive ion channel, piezo1 in epithelial cells. Opening of the piezo1 channel by mechanical or chemical stimulation also induced a strong Ca2+ influx in the endometrial epithelial cells.

Here, we aim to assess the importance of the trypsin- and piezo1- induced Ca2+ influx for inducing processes like decidualization and blastocyst adhesion. Moreover, we will develop and validate an endometrial organoid model containing epithelial and stromal cells. The outcome of this project will strongly improve the fundamental background on implantation.