A confocal microscope image showing the proteins of a human embryo that are 9 days old in various colors. Proteins associated with embryonic stem cells are shown in green, while early tissues and DNA are displayed in pink and blue, respectively. Muscle is red. The scale bar is 100μm (micrometers; 1μm is one-millionth of a meter)./Courtesy of Catalonia Institute of Bioengineering (IBEC)

Scientists have captured the process of an embryo implanting in the uterus for the first time. Contrary to expectations, it has been revealed that the human embryo penetrates deeply into the uterine lining. This video is expected to aid in infertility treatment by showing the first stage of pregnancy, which has remained shrouded in mystery until now.

Dr. Samuel Ojosnegros and his research team at the Institute for Bioengineering of Catalonia (IBEC) stated on the 16th that they captured the implantation process of a human embryo in a 3D (three-dimensional) artificial uterine environment in real time.

Implantation is the process where a fertilized egg (embryo) attaches to the uterine lining about 6 to 12 days after ovulation, and passing through this stage is crucial for confirming pregnancy. In fact, failures in embryonic implantation account for 60% of miscarriages. The research team noted that this study's results could help understand the principles of the embryonic implantation process, providing significant benefits for improving infertility and optimizing assisted reproductive technologies.

The human embryo contracts./Courtesy of Catalonia Institute of Bioengineering (IBEC)

◇Embryo entering by dissolving and tearing the lining

Scientists at the Institute for Bioengineering of Catalonia developed a 3D artificial uterus where embryos can implant. It was made from gel containing collagen, a protein that forms skin and muscle, and uterine tissue. The gel refers to particles dispersed in a liquid that solidify into a mesh structure. Think of jelly or pudding. If the solid part is surrounded by water, it is called hydrogel; if by air, it is called aerogel.

The research team injected human and mouse embryos into the artificial uterus and observed the implantation process using fluorescence microscopy. They took microscopic images every 20 minutes over a duration of 16 to 24 hours and compiled these images into a video.

As a result of the experiment, mouse embryos adhered to the surface of the uterine lining. When a mouse embryo contacts the uterus, it exerts force to attach to the surface. The uterus then folds around the embryo. In contrast, human embryos were found to fully penetrate the lining before growing from the inside out.

The research team explained that this indicates that human embryos secrete enzymes that degrade the surrounding lining during the implantation process. However, force is also needed for the embryo to penetrate the uterus. The fibrous tissue of the uterine lining is filled with tough collagen proteins that make up skin, muscle, bone, tendon, and cartilage.

The human embryo exerts force on the artificial uterine lining tissue, causing the tissue to separate./Courtesy of Catalonia Institute of Bioengineering (IBEC)

Dr. Ojosnegros, the correspondence author of the paper, observed that it exerts significant force as the human embryo burrows into the uterus and said, "It is known that many women experience abdominal pain and light bleeding during implantation, but this process itself has not been observed previously."

Once the embryo enters the uterine lining, it finally becomes one with the mother. Dr. Ojosnegros stated, "The embryo opens a path through the collagenous fibrous lining and begins to form tissues connected to the mother's blood vessels to receive nutrients."

Given that the implantation process has been visually confirmed, the research team expects it will greatly aid in infertility treatment in the future. For example, new criteria could be established to select embryos suitable for implantation after artificial insemination, thereby increasing pregnancy rates.

Dexeus University Hospital in Barcelona provided human embryos for this study. The Barcelona Stem Cell Bank (IDIBELL), Barcelona University, the Biomedical Research Networking Center (CIBER) in Madrid, and Tel Aviv University in Israel also participated.

References

Science Advances (2025), DOI: https://doi.org/10.1038/d41586-025-02627-2

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