Researchers have created the lining of the uterus in a dish that promises to shed light on the mysterious early stages of human pregnancy and disorders that can lead to miscarriage and medical complications.
In laboratory experiments, early-stage human embryos were donated in pairs after ECO the treatment successfully implanted into the artificial membrane and began releasing key compounds, such as the hormone that causes the blue line to appear on positive pregnancy tests.
This approach allowed scientists to eavesdrop on the chemical exchange that occurs between the embryo and the uterine lining as it implants and begins to feed in the early weeks of pregnancy.
“It's incredible to see this,” said Dr Peter Rugg-Gunn, senior author of the study and team leader at the Babraham Institute in Cambridge. “Previously, we only had images of this critical stage of pregnancy. This opens up many new directions for us.”
Implantation occurs about a week after fertilization, when the developing embryo attaches and then implants itself into the wall of the uterus. This is a crucial phase of pregnancy, but the process is poorly understood because it is very difficult to observe. Most of what is known comes from studies of hysterectomies performed in early pregnancy more than half a century ago.
To create an exact replica of the uterine lining, Rugg-Gunn and his colleagues obtained uterine tissue from healthy women who donated biopsy samples. From this, the scientists isolated two different types of cells: stromal cells, which provide structural support to the uterine lining, and epithelial cells, which form the surface of the uterine lining. They encapsulated stromal cells in a biodegradable material called a hydrogel and placed epithelial cells on top.
Researchers tested artificial uterine lining on donor embryos obtained through early-stage IVF. Sign up for Cell magazineThey describe how microscopic balls of cells attached and implanted as expected. They then increased secretion of the hormone human chorionic gonadotropin (hCG), a biochemical marker detected by pregnancy tests, as well as other compounds associated with pregnancy.
This method allowed scientists to monitor the growth of embryos for 14 days after fertilization, which is the legal limit for research. During this process, embryos develop specialized cells and other cells involved in the growth of the placenta.
To further understand this process, scientists zoomed in on the sites where embryos implanted in the artificial uterine lining and deciphered the molecular signals that were transmitted back and forth. Such signals are critical to achieving and maintaining a healthy pregnancy.
Now scientists will use this approach to figure out how pregnancy happens and what can go wrong. “We know that half of all embryos don't implant, and we have no idea why,” Rugg-Gunn said. Finding answers can provide a much-needed boost to IVF success.
Further experiments will reveal what happens after implantation, when the placenta begins to form. Many serious pregnancy complications are thought to occur at this stage. In the study, scientists used a chemical to block a specific signal between the embryo and the lining, causing severe defects in the tissue that forms the placenta and demonstrating its ability to test the impact of signaling problems.
IN separate study In the journal, Chinese researchers created their own replica of the uterine lining and identified drugs that could improve implantation rates in patients with recurrent implantation failure (RIF), where good quality IVF embryos fail to achieve pregnancy.
John Aplin, professor of reproductive medicine at the University of Manchester, said implantation rates had remained consistently low during more than 40 years of assisted reproduction.
“Once the embryo is implanted, a program is initiated to begin the development of the placenta, which will supply the fetus with nutrients and oxygen,” he said. “The earliest stages are critical for pregnancy development, are understudied and often fail. This work will explore treatments to improve implantation success.”
