Human embryo implantation recorded in real time for the first time

Researchers at the Institute for Bioengineering of Catalonia (IBEC) in collaboration with the Dexeus University Hospital have captured unparalleled images of a human embryo implanting. This is the first time that the process has been recorded in real time and in 3D.

Failure of the implantation process in the uterus is one of the main causes of infertility, accounting for 60% of spontaneous abortions. Until now, it had not been possible to observe this process in humans in real time, and the limited available information came from still images taken at specific moments during the process.

'We have observed that human embryos burrow into the uterus, exerting considerable force during the process. These forces are necessary because the embryos must be able to invade the uterine tissue, becoming completely integrated with it. It is a surprisingly invasive process. Although it is known that many women experience abdominal pain and slight bleeding during implantation, the process itself had never been observed before," explains Samuel Ojosnegros, principal investigator of the IBEC's Bioengineering for Reproductive Health group and leader of the study.

To advance during implantation, the embryo releases enzymes that break down the surrounding tissue. However, it is also known that force is required in order to penetrate the underlying layers of the uterus. This fibrous tissue is filled with collagen, a rigid protein that also forms tendons and cartilage. “The embryo opens a path through this structure and begins to form specialised tissues that connect to the mother's blood vessels in order to feed,” adds Ojosnegros.

The research team's results reveal that human embryos exert traction forces on their environment, remodelling it. "We observe that the embryo pulls on the uterine matrix, moving and reorganising it. It also reacts to external force cues. We hypothesise that contractions occurring in vivo may influence embryo implantation,” explains Amélie Godeau, a researcher in the Ojosnegros group and co-first author of the study. Thus, effective embryo invasion is associated with optimal matrix displacement, highlighting the importance of these forces in the implantation process.

Improving our understanding of the implantation process could have a significant impact on fertility rates, embryo quality and the time taken to conceive through assisted reproduction.

A platform for studying implantation in the laboratory

To carry out the study, the IBEC research team developed a platform that allows embryos to implant outside the uterus under controlled conditions. This enables real-time fluorescence imaging and analysis of the embryo's mechanical interactions with its environment. The platform is based on a gel composed of an artificial matrix formed by collagen, which is abundant in uterine tissue, and various proteins necessary for embryo development.

Experiments were carried out with both human and mouse embryos to allow comparison of the two implantation processes. When the mouse embryo comes into contact with the uterus, it exerts forces to adhere to its surface. The uterus then adapts by folding around the embryo, enveloping it in a uterine crypt. In contrast, the human embryo moves inward and penetrates the uterine tissues completely. Once there, it begins to grow radially from the inside out.

“Our platform has enabled us to quantify the dynamics of embryo implantation and determine the mechanical footprint of the forces used in this complex process in real time,” concludes Anna Seriola, IBEC researcher and co-first author of the study.

This study was conducted in collaboration with the Dexeus University Hospital (which donated all the embryos used in this study), the Biomimetic Systems for Cell Engineering group at IBEC, led by Elena Martínez, as well as other institutions such as the Barcelona Stem Cell Bank (IDIBELL), the University of Barcelona (UB), the Tel Aviv University, the Biomedical Research Networking Centre (CIBER) and the Institute for Research in Biomedical (IRB Barcelona).