Confocal microscopy image of a 9-day-old human embryo. Specific proteins and cellular structures have been coloured in the image: OCT4 (green), which is related to embryonic stem cells; GATA6 (magenta), which is associated with early tissue formation; DAPI (blue), which marks the DNA in the nuclei; and phalloidin (red), which reveals the actin cytoskeleton. Credit: Institute for Bioengineering of Catalonia (IBEC)
Researchers have captured 3D images of the moment a human embryo implanted itself in a system that simulates the uterine environment, helping scientists build a better understanding of what happens during the implantation process.
It had previously not been possible to observe the implantation process in humans in real time, with traditional methods limited to still images taken at specific moments during the process.
In Australia, almost 109,000 in vitro fertilisation (IVF) cycles were performed in 2022, with the live birth rate per embryo transfer cycle increasing to 29.9% from 27.3% in 2018. The researchers hope that improving the understanding of the implantation process could have a significant impact on fertility rates and the time taken to conceive through assisted reproduction like IVF.
During implantation, an embryo releases enzymes that break down the uterine tissue which allows it to implant. However, scientists there is another force that is used to break down the underlying layers of the uterus that are filled with collagen.
“Although it is known that many women experience abdominal pain and slight bleeding during implantation, the process itself had never been observed before” says lead author Samuel Ojosnegros, who leads the Bioengineering for Reproductive Health group at the Institute for Bioengineering of Catalonia (IBEC), Spain.
The real-time fluorescence imaging in this research shows that human embryos exert traction forces on their environment throughout this process.
“We observe that the embryo pulls on the uterine matrix, moving and reorganising it. It also reacts to external force cues,” says Amélie Godeau, a co-author of the study and researcher in Ojosnegros’s group.
“We hypothesise that contractions occurring in vivo may influence embryo implantation.”
These embryo forces play an important role in the implantation process for successful embedding.
“These forces are necessary because the embryos must be able to invade the uterine tissue, becoming completely integrated with it,” says Ojosnegros.
The researchers developed a platform that allowed embryos to implant under controlled conditions outside of the uterus. This platform was created using a gel composed of an artificial matrix of proteins required for embryo development and collagen.
“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,” says Anna Seriola, co-first author of the study from IBEC.
The research team performed the experiment on both human and mouse embryos to compare the implantation process between them.
They found when the mouse embryos were forced to adhere to the surface of the uterus, it adapts by folding around and surrounding the embryo.
But in humans, the embryo moves towards the tissue where it doesn’t just adhere but penetrates the uterine tissue completely. The embryo then begins to grow from the inside out.
“It is a surprisingly invasive process,” says Ojosnegros.
“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.”
The study is available to read in Science Advances.