Modelling embryo-endometrial crosstalk to reduce time to pregnancy (in times of health and pandemic)

Embryo implantation is a bottleneck for pregnancy in many couples with a desire to conceive. Because of obvious ethical concerns regarding the use of human embryos for research and the unethical study of pregnancy in vivo, scientific advancement in the field is limited. The need to better understand the crosstalk between the embryo and the endometrium is crucial for IVF patients’ management. In particular, the latest SARS-CoV-2 pandemic and the following treatment postponements had a concerning impact on the time to pregnancy in IVF clinics. To identify crucial pathways and proteins during pre-and peri-implantation development more in vitro study is required. More precisely the interaction between the endometrium and the blastocyst is an important field to focus on. Implantation consists of three steps: apposition, adhesion and invasion. In the first part of this thesis, we studied the role of CD147, a well-described player for implantation in mice, using a 2-dimensional model for embryo adhesion. Ishikawa cells and human blastocysts were co-cultured for 48 hoursfrom6 to8 days post fertilisation with a CD147 receptor blocker. This resulted in impaired adhesion of the blastocysts indicating a crucial role of the protein during the initiation of implantation. To investigate the role of trophectoderm during implantation we analysed RNA of human blastocysts with Next Generation Sequencing and linked the expression to the implantation capacity of the embryo in vitro. To study the process of invasion, we set up a new multicellular 3D model which sustained embryo development until 11 days post fertilisation. We identified differential RNA expression when comparing embryos that succeeded or failed to implant in the model. Further investigation is required to study each new pathway and gene individually. In the second part of this thesis, we investigated the impact of SARS-CoV-2 infection on human reproduction. Firstly, we reported the presence of viral receptors on the membrane of human cumulus cells, oocytes and blastocysts. This highlights the vulnerability of the cells to the virus. Secondly, we investigated the transmission of the virus in vivo to reproductive tissues in IVF patients with an active infection. We could report a viral absence in cumulus cells, follicular fluid and endometrial samples of infected patients, reassuring the safety of ART treatment during the COVID-19pandemic. In conclusion, we studied the process of implantation in human embryos using a well-established model to study adhesion and we developed a new multicellular 3D model to study invasion in vitro. We proved the role of CD147 in adhesion and identified new key players for invasion. In addition, we demonstrated the vulnerability of embryos to SARS-CoV-2 infection, but we confirmed that in female IVF patients with an active infection there is no transmission of the virus to reproductive tissues. The results of this thesis will contribute to progress in the management of IVF patients in times of health and COVID-19 pandemic.

ISBN:9789464443394

Jaar van publicatie:2022

Trefwoorden:embryo-endometrial crosstalk, pregnancy, Embryo Implantation, IVF

Toegankelijkheid:Embargoed