Implantation, one of the most poorly understood phases of early human development, occurs in the depths of the womb, at a time when embryos are microscopic and well out of reach. Until recently, much of what was known about this critical moment came from limited indirect evidence. Babraham University researchers have taken that leap ahead by creating an artificial model of the lining of the human womb. For the first time, it will enable scientists to closely observe how very early-stage human embryos behave when they first attach and embed themselves. This allows researchers to explore, for the first time outside the body, those hidden biological processes that shape early pregnancy and determine success or failure.
Scientists create a womb-like lining for embryos to attach and grow
For scientists to investigate implantation in the lab, they had to create a system that mimicked the structure and function of the uterine lining, or endometrium. The first step was to harvest samples of uterine tissue from women known to have healthy tissues. Two cell types were isolated from the tissue: stromal cells, which comprise the support matrix of the lining; and epithelial cells, which line the part of the lining where implantation of the embryo occurs. The stromal cells were packed into a biodegradable hydrogel to replicate their natural surroundings, and epithelial cells on top mimicked the lining of the womb.In the laboratory model, the embryos at the early stages of development that were donated after IVF procedures were able to implant properly on the bioreactor lining. Following the successful implantation of the embryos, they started secreting human chorionic gonadotropin (hCG) and other factors that would normally be secreted during pregnancy. This would enable the monitoring of the development of embryos for a maximum of 14 days after fertilization, though this is the limit for research in many jurisdictions of the world. At this time, the embryos would begin to differentiate into specialized cells and placenta-contributing cells.
How embryos and the womb lining “talk” during early pregnancy
“Chatter” communication between the embryo and the uterine lining is one of the major insights that came from the study. As the embryos were implanted into the uterus, they communicated with the endometrium in chemical signals that helped to bring them into contact and for the development of tissues and the formation of the placenta. The system enabled the scientists to study the chemical signals that took place between the embryos and the endometrium. When certain chemical signals were inhibited, the tissue that gave rise to the placenta was defective.Failure of implantation is one of the causes of the failure of embryos to initiate a pregnancy, although the causes have not been well understood. Soft tissues can be replicated to simulate the uterine lining, allowing the interactions of the embryos to be observed, thereby allowing the causes of the failure of implantation to be understood and solutions to be found. In China, research has been conducted that demonstrates the effectiveness of certain medications in increasing the chances of successful implantation in patients with repeated implantation failure (RIF).
