Embryo protein may warn before miscarriage and pre-eclampsia
It’s a sticky business. Scientists have uncovered how embryos stick to the uterus in the first week of life. The discovery might one day help improve treatments for recurrent miscarriages and pre-eclampsia, a life-threatening elevation of maternal blood pressure.
After a human egg is fertilised, it tumbles down the mother’s fallopian tubes and into her uterus. There it makes itself comfy by sticking to the wall of the uterus, then burying itself under the wall’s lining.
Now, Harry Moore and Bikem Soygur at the University of Sheffield, UK, have shown that a protein called syncytin-1, produced by a gene that humans gained from viruses 25 million years ago, probably plays a vital role in this process.
Syncytin-1 is known to help embryos burrow into the uterus, as well as form a placenta – a process that begins around five to seven days after fertilisation. But Moore and Soygur found that the protein is secreted earlier than this, suggesting that it also helps embryos stick to the uterus.
It is important to have a better understanding of these early days of development because they can influence how a pregnancy progresses, says Moore. “There’s a feeling between scientists that a lot of conditions, such as recurrent miscarriage and pre-eclampsia, are caused by the very earliest stages of embryo implantation and that process not happening correctly.”
Moore and Soygur studied 20 human embryos donated by women undergoing IVF. They grew the embryos for up to five days until they became blastocysts – bundles of around 100 cells.
They then preserved the blastocysts and stained them with antibodies that make syncytin-1 fluoresce. They found that cells around the outside of the embryo begin to produce syncytin-1 between four and five days after fertilisation.
Previous research has shown that syncytin-1 makes different cell types stick together. Moore thinks that the protein is produced this early to help the embryo stick to the uterus. Syncytin-1 then stimulates the release of enzymes that break down the uterine lining, allowing the blastocyst to implant itself and start to develop a placenta.
“Syncytin-1 is sort of extraordinary,” says Moore. We gained this protein, he says, from our dim and distant past.
“Using genetic markers, people have been able to go far back and show that there were retroviral infections that were responsible for the creation of the placenta in mammals,” says Moore. “For humans, it goes back to the syncytin-1 gene, which invaded our primate ancestors 25 million years ago. That led to the evolution of a very efficient placenta in women.”
Moore says that it may be possible to use their results to develop blood tests that identify embryos that haven’t implanted properly. This would enable us to spot mothers who might be at risk of certain conditions and to help develop appropriate therapies.
Janet Rossant, a developmental biologist at the University of Toronto in Ontario, Canada, says that the syncytin gene is very interesting and has been known for some time to be important for the development of the placenta and a potential target for conditions such as pre-eclampsia.
However, the new study does not have direct proof of a role for the protein in implantation, she says.
Moore would like to address this in future experiments, to see if there is a direct association between levels of syncytin-1 expressed by the embryo and its ability to implant properly. “Ideally, we’d then like to compare this to any conditions that might arise,” he says.
Journal reference: Human Reproduction, DOI: 10.1093/humrep/dew097