Izumo-Juno Proteins Essential For Fertilisation

Interacting proteins on the surfaces of the sperm and the egg have been discovered which are fundamental to begin mammalian life. These proteins, found by Wellcome Trust Sanger Institute researchers, allow the sperm and egg to recognize one another. The finding opens new doors towards better fertility treatments as well as the development of new contraceptives.

When an egg and a sperm identify each other and fuse together to form an embryo is when fertilisation is said to occur, and when a new genetically distinct organism is formed.

The Izumo protein expressed on the sperm that recognises the egg was identified in 2005 by Japanese researchers. They dubbed it Izumo, after the Japanese marriage shrine Izumo-Taisha. Its counterpart on the egg remained unknown until now.

Juno, Roman Goddess of Fertility

The team discovered a single protein which paired with Izumo and is necessary for fertilisation. The protein is named Juno after the Roman Goddess of fertility and marriage.

“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,” said senior author Dr Gavin Wright. “Without this essential interaction, fertilisation just cannot happen. We may be able to use this discovery to improve fertility treatments and develop new contraceptives.”

A synthetic version of the Izumo protein was created and scientists used this to identify binding partners on the surface of the egg. With this method, they discovered that Izumo on the sperm interacted with Juno on the surface of the egg to begin fertilisation.

Mice that lacked the Juno protein on the surface of their eggs were developed by the team. The mice were infertile and their eggs did not fuse with normal sperm. This verified 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.

Essential Interaction for Sperm-egg Recognition

“The Izumo-Juno pairing is the first known essential interaction for sperm-egg recognition in any organism,” says Dr Enrica Bianchi, first author. “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 researchers also found that after the initial fertilisation step, there is an abrupt loss of the Juno protein from the surface of the egg. It became virtually undetectable after just 40 minutes.

This disappearance could explain why the egg, once fertilised by the first sperm cell, shuts down its ability to recognise further sperm. This prevents the formation of embryos with more than one sperm cell that would otherwise have too many chromosomes and die.

The team is screening infertile women to investigate whether defects in the Juno receptor are a cause of infertility. If this is the case, 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.

Reference:

Juno is the egg Izumo receptor and is essential for mammalian fertilization
Bianchi E, Doe B, Goulding D, Wright GJ
Nature 2014 DOI: 10.1038/nature13203

Inoue, N., Ikawa, M., Isotani, A. & Okabe, M.
The immunoglobulin superfamily protein Izumo is required for sperm to fuse with eggs.
Nature 434, 234–238 (2005)

Image courtesy of Ed Uthman, Creative Commons