In a first-ever move, 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 in real time and 3D. The work was published in the journal Science Advances.Failure of the implantation process in the uterus is one of the leading causes of infertility, accounting for 60% of spontaneous abortions. Until now, it had not been possible to observe the process in humans in real time.“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,” explained Samuel Ojosnegros, leader of the study and principal investigator of the IBEC’s Bioengineering for Reproductive Health group.To advance during implantation, the embryo releases enzymes that break down the surrounding tissue. This force is required to penetrate the underlying layers of the uterus. This fibrous tissue is filled with collagen that also forms tendons and cartilage.“The embryo opens a path through this structure and begins to form specialized tissues that connect to the mother’s blood vessels in order to feed,” added Ojosnegros.
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To carry out the study, the IBEC research team developed a platform that allows embryos to implant outside the uterus under controlled conditions. This enabled real-time fluorescence imaging and analysis of the embryo’s mechanical interactions with its environment.They carried out experiments with both human and mouse embryos to compare the two implantation processes. While the mouse uterus folds itself around the embryo adhered to its surface to form a uterine crypt, the human embryo moves inwards and penetrates the uterine tissues completely. Then it begins to glow radially from the inside out.The 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 reorganizing it. It also reacts to external force cues. We hypothesize that contractions occurring in vivo may influence embryo implantation,” explained Amélie Godeau, a researcher in the Ojosnegros group and co-first author of the study.The real-time images improve the understanding of the implantation process and thus could have a significant impact on fertility rates, embryo quality and the time taken to conceive through assisted reproduction.