Mammal Fertilization begins with Juno and Izumo

Fertility scientists have solved the mystery of how mammal eggs know when sperm has come into contact with them, new research suggests.

Researchers announced they have found the companion to the Izumo protein in sperm that recognizes an egg. The egg's version of this protein, dubbed Juno, was described Wednesday in the journal Nature.

The Izumo protein, named after a Japanese marriage shrine, was described in 2005; Juno is named after the Roman goddess of fertility an marriage. Both proteins are essential for the reproduction in mammals, including humans, the researchers said.

"We have solved a long-standing mystery in biology by identifying the molecules displayed on all sperm and egg that must bind each other at the moment we were conceived," said senior study author Gavin Wright from the Wellcome Trust Sanger Institute. "Without this essential interaction, fertilization just cannot happen. We may be able to use this discovery to improve fertility treatments and develop new contraceptives."

To identify what was interacting with the Izumo protein on the surface of eggs, the researchers created an artificial Izumo and used it to identify binding partners on the surface of the egg. By doing this they were able to observe Izumo on sperm interacting with Juno on eggs.

To test the importance of Juno, the researchers bred mice whose eggs lacked the protein. These mice all turned out to be infertile and their eggs did not fuse with normal sperm, which the researchers say highlights how essential Juno is for natural reproduction.

A similar test also found that male mice lacking Izumo are also infertile.

"The Izumo-Juno pairing is the first known essential interaction for sperm-egg recognition in any organism," said first study author Enrica Bianchi, of the Wellcome Trust Sanger Institute. "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."

Probing deeper into the biomechanics of the Izumo-Juno paring, the researchers found that after the initial fertilization step, there is a sudden loss of Juno protein from the surface of the egg. After just 40 minutes, there is virtually no trace of Juno proteins on a fertilized egg.

The researchers suggest that this could be way egg cells stop recognizing sperm after having become fertilized.

In the future, the relationship between Izumo and Juno proteins could play a role in infertility treatments, the researchers said.