In 2005, researchers in Japan discovered a protein on the surface of sperm that recognizes the egg so they can fuse to form an embryo. They called it Izumo, after a Japanese marriage shrine. Now, researchers in the UK have found its mate on the egg, and called it Juno, after the Roman goddess of fertility and marriage.
And they confirmed that the meeting of Izumo and Juno is the first step to creating a new, genetically distinct individual in mammals.
The researchers, from the Wellcome Trust Sanger Institute in Cambridge, UK, report their findings in the journal Nature. Senior author Dr. Gavin Wright, who leads the Institute's Cell Surface Signalling Laboratory, says:
"We have solved a long-standing mystery in biology by identifying the molecules displayed on the sperm and egg which must bind each other at the moment we were conceived. Without this essential interaction, fertilisation just cannot happen."
He and his fellow researchers hope the discovery will lead to improvements in fertility treatments and new contraceptives.
As a first step, the team developed an artificial version of Izumo and used it to detect binding partners on the surface of a mouse egg. They found it bound to folate receptor 4 (Folr4) and renamed it Juno.
They then engineered a strain of mice where the females lacked the Juno protein on the surface of their eggs. These mice were infertile and their eggs did not fuse with normal sperm. This showed Juno was essential to that step and for female fertility.
The team then ran the experiment the other way - they bred mice to lack the Izumo protein on the surface of their sperm and showed they were infertile.
They also found that once fertilized, eggs shed the normally abundant Juno rapidly from their surfaces, thus ensuring they fuse only with a single sperm. Within 40 minutes, the protein is virtually undetectable on the cell surfaces. If the egg cell fuses with more than one sperm, it has too many chromosomes and dies.
The team explains their findings in the video below:
Discovery took several tries, because the binding of Izumo and Juno is weak
It took several attempts to make these discoveries, and they had to keep redesigning their experiments, because, as first author Dr. Enrica Bianchi, also of the Cell Surface Signalling Laboratory, explains:
"The binding of the two proteins is very weak, which probably explains why this has remained a mystery until now. Previous work in the laboratory led us to expect the interaction to be weak, and this then guided the design of our experiments, and, after a lot of effort, it finally worked."
The team is now screening infertile women to find if they have any defects in their Juno receptors. If there is a link between Juno defects and infertility, then a simple genetic test could provide valuable information for helping infertile women and their doctors choose the best treatment.
In September 2013, Medical News Today learned a reason why some embryos do not implant in the uterus. Teams from the UK and the Netherlands showed that the uterus performs "quality control" on a new embryo before deciding whether to accept it. They hope the finding will lead to improvements in the success rate of IVF.