Researchers have created the lining of a womb in a dish, which promises to shed light on the mysterious early stages of human pregnancy and the glitches that can lead to miscarriage and medical complications.
In laboratory experiments, early-stage human embryos donated from couples after IVF treatment successfully implanted into the engineered lining and began to churn out key compounds, such as the hormone that results in a blue line on positive pregnancy tests.
The approach allowed scientists to eavesdrop on the chemical chatter that arises between the embryo and the womb lining as it embeds and begins to be nourished in the first weeks of gestation.
“It’s incredible to see it,” said Dr Peter Rugg-Gunn, a senior author on the study and group leader at the Babraham Institute in Cambridge. “Previously we’ve only had snapshots of this critical stage of pregnancy. This opens up a lot of new directions for us.”
Implantation takes place a week or so after fertilisation when the developing embryo attaches and then embeds itself into the uterus wall. It is a crucial phase in pregnancy, but the process is poorly understood because it is so hard to observe. Much of what is known comes from studies of hysterectomies that were performed in early pregnancy more than half a century ago.
To build the replica womb 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 that give structural support to the womb lining, and epithelial cells, which form the lining’s surface. They encapsulated the stromal cells in a biodegradable material called a hydrogel and put the epithelial cells on top.
The researchers tested the engineered womb lining with donated early-stage IVF embryos. Writing in the journal Cell, they describe how the microscopic balls of cells attached and implanted as hoped. They then ramped up secretion of a hormone called human chorionic gonadotropin (hCG), the biochemical marker detected by pregnancy tests, along with other pregnancy-related compounds.
The technique enabled scientists to watch embryos grow for up to 14 days post-fertilisation, the legal limit for research. During the process, the embryos formed specialised cells and other cells involved in the growth of the placenta.
To understand the process more deeply, the scientists zoomed in on the spots where embryos had embedded in the engineered womb lining and decoded the molecular signals that passed back and forth. Such signals are critical for achieving and maintaining a healthy pregnancy.
Scientists will now use the approach to investigate how pregnancies become established and what can go awry. “We know that half of all embryos fail to implant and we have no idea why,” Rugg-Gunn said. Finding answers could provide a much-needed boost to IVF success rates.
Further experiments will explore what happens after implantation when the placenta starts to form. Many serious complications of pregnancy are thought to arise at this stage. In the study, the researchers used a chemical to block a particular signal between the embryo and the lining, producing severe defects in the tissue that forms the placenta, demonstrating its power for testing the impact of signalling problems.
In a separate study in the journal, Chinese researchers created their own replica womb lining and identified drugs that might improve implantation rates in patients with recurrent implantation failure (RIF), where good-quality IVF embryos fail to establish a pregnancy.
John Aplin, a professor of reproductive medicine at the University of Manchester, said that during 40-plus years of assisted reproduction, implantation rates had remained stubbornly low.
“As the embryo implants, a programme is initiated to begin development of the placenta, which will supply nutrients and oxygen to the foetus,” he said. “The earliest stages are crucial to the progression of the pregnancy, are not well understood, and frequently fail. This work will allow treatments to be explored that seek to improve implantation efficiency.”
