Juno, a long-sought protein named after the Roman goddess of fertility and marriage, has been discovered on the surface of the mammalian egg. This protein recognizes its sperm-riding counterpart, Izumo, at the very first interaction between egg and sperm. Although Juno and Izumo bind to each other weakly, the union is fateful, as it results in fertilization.
Izumo, which is named after a Japanese marriage shrine, was discovered by Japanese researchers in 2005. But its binding partner on the egg remained a mystery until researchers at the Wellcome Trust Sanger Institute identified the egg’s Izumo receptor, folate receptor 4 (Folr4). This discovery prompted the researchers to suggest changing Folr4 protein’s name to the more felicitous Juno.
Juno was initially found in mouse oocytes, but the researchers subsequently determined that the Izumo-Juno interaction is conserved within mammalian species, including humans. These findings appeared April 16 in Nature, in an article entitled “Juno is the egg Izumo receptor and is essential for mammalian fertilization.”
“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 Gavin Wright, D. Phil., senior author from the 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.”
The scientists created an artificial version of the Izumo protein and used this to identify binding partners on the surface of the egg. Using this approach, they discovered that Izumo on the sperm interacted with Juno on the surface of the egg to initiate fertilization.
The team developed mice that lacked the Juno protein on the surface of their eggs. These mice were infertile and their eggs did not fuse with normal sperm, highlighting that the Juno protein is essential for fertility in female mice. In the same way, male mice lacking the Izumo protein are also infertile, highlighting its essential role in male fertility.
In their paper, the authors provided additional details. For example, they wrote: “Comparing our findings with recent advances in the molecular understanding of cellular fusion in other biological contexts suggests that the Izumo1–Juno interaction performs a necessary adhesion step rather than acting as a membrane ‘fusogen.’”
In addition, the researchers speculated about mechanisms that could explain how the egg, once fertilized by the first sperm cell, can shut down its ability to recognize further sperm. Juno, the researchers noted, is quickly lost after fertilization, becoming undetectable in about 40 minutes: “One possibility is that because Juno is shed as vesicles after fertilization, this creates a zone of ‘decoy eggs’ confined within the perivitelline space that could bind to and efficiently neutralize incoming acrosome-reacted sperm to increase the potency of the spermblock.”
The team is now screening infertile women to understand whether defects in the Juno receptor are a cause of infertility. If it is, then a simple genetic screening test could help inform the appropriate treatment for women struggling to conceive naturally by reducing the expense and stress often involved in assisted fertility treatments.