Protein discovery on human eggs may shed light on unexplained infertility
A fundamental step in human fertilisation has been discovered by researchers who say it may offer new insights into unexplained infertility.
Experts have identified a new protein that is found on the surface of human eggs. Nicknamed Maia, after the Greek goddess of motherhood, the protein appears to be involved in the fusion of sperm and eggs.
Prof Harry Moore, of the University of Sheffield, who was the lead investigator of the study, said the findings may help to shed light on cases where fertilisation fails during IVF for unknown reasons.
He said tests could be developed to explore whether an individual’s sperm is unable to bind to Maia, or whether an individual’s eggs do not have the protein on their surface.
“These tests are possible; whether they become common is difficult to say,” he said, adding that identifying such problems could help to direct clinicians to techniques that may overcome the difficulty.
Writing in the journal Science Advances, researchers from countries including the UK, the Czech Republic and Japan report how they began the work by attaching 13m different protein segments, or peptides, to the surface of synthetic microbeads. Each bead was around the same size as a human egg, and attached to a different peptide.
When the team incubated human sperm with these beads, they found less than one in 1,000 bound to the sperm. “You could identify them because the sperm caused the beads to spin round and round as it is binding to it,” said Moore.
Through further work the team were able to identify the peptide that was attached to the surface of these beads, and hence the full protein it related to. They were also able to identify the gene that gives rise to this “Maia” protein in the body.
Additional experiments showed that Maia is present on the surface of human eggs, while work with hamster eggs lacking an outer matrix showed that if Maia is blocked, for example by antibodies, sperm would not be able to fuse with the eggs.
The importance of Maia was underlined by other experiments, including work in which the gene for the Maia was introduced to non-egg human cells so that they produced the protein on their surface. When these cells were exposed to human sperm in a dish, the sperm bound and fused to the cells in the same way as natural fertilisation.
“It showed you that this protein was important because otherwise [the cells] wouldn’t have fused together,” Moore said.
The team then used molecular modelling and other techniques to examine the role of Maia.
The approach confirmed previous findings that sperm initially bind to a protein on the surface of the egg called Juno, but also suggested that sperm subsequently detach from Juno and bind to Maia. Maia then collapses into the egg membrane, drawing the sperm into the cell.
Prof Gavin Wright, of the University of York, who was not involved in the work, welcomed the study, noting that it was a surprising discovery given Maia is more often thought to be a component of the immune system.
He said the modelling work raised additional questions that needed to be investigated. “Infertility is a painful problem affecting an increasing number of couples, and although this research may not provide any immediate benefits for diagnosis or treatments, it will contribute to a better understanding of this fascinating and fundamental biological process,” he said.