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Author Topic: Fertility mystery solved: protein discovered that joins sperm with eggs  (Read 10868 times)
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The Guardian, Wednesday 16 April 2014 18.02 BST

British scientists' identification of Juno molecule opens door to new developments in fertility treatment and contraception
A fundamental key to fertility has been uncovered by British scientists with the discovery of an elusive protein that allows eggs and sperm to join together.
The molecule named Juno after the Roman goddess of fertility sits on the egg surface and binds with a male partner on a fertilising sperm cell.
Japanese researchers identified the sperm protein in 2005, sparking a decade-long hunt for its "mate".
Understanding the process by which the molecules interact opens the door to new developments in fertility treatment and contraception.
"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 lead researcher Dr Gavin Wright, from the Welcome Trust Sanger Institute in Hinxton, Cambridgshire.
"Without this essential interaction, fertilisation just cannot happen. We may be able to use this discovery to improve fertility treatments and develop new contraceptives."
The Sanger Institute team first created an artificial version of the sperm protein, called Izumo1 after a Japanese marriage shrine.
This was then used to search for binding partners on the surface of the egg. A single protein, Juno, was identified as Izumo1's "other half".
Juno's importance to fertility was revealed by female laboratory mice engineered to produce eggs lacking the molecule.
All the animals were infertile, their eggs incapable of fusing with normal sperm. Male mice missing Izumo1 were also unable to conceive, highlighting this protein's role in male fertility.
The research, reported in the journal Nature, also suggests that Juno plays a role in preventing additional sperm fusing with an already fertilised egg.
"The Izumo-Juno pairing is the first known essential interaction for sperm-egg recognition in any organism," said co-author Dr Enrica Bianchi, also from the Sanger Institute. "The binding of the two proteins is very weak, which probably explains why this has remained a mystery until now."
After the initial binding of sperm and egg, Juno bows out, becoming virtually undetectable after 40 minutes, the scientists found.
This may help explain why as soon as an egg is fertilised by one sperm cell it puts up a barrier against others.
Fertilisation involving more than one sperm would lead to the formation of abnormal doomed embryos with too many chromosomes.
Juno belongs to a family of "folate receptor" proteins, but unlike its brethren is unable to bind to folic acid. The researchers looked at three folate receptors, and found that only Juno interacted with Izumo1.
The scientists are now screening infertile women to see whether Juno defects underlie their condition.
If they do, a simple genetic screening test could help doctors provide them with the most appropriate treatment while avoiding wasteful expense and stress.
Regular In-Vitro Fertilisation (IVF) treatment, with sperm randomly fertilising eggs in a laboratory dish, could not work without Juno.
However, it may be possible to bypass the natural mating of Izumo1 and Juno using intra-cytoplasmic sperm injection (Icsi). This is an increasingly popular method of IVF which involves injecting a sperm directly into an egg.
Leading fertility expert Dr Allan Pacey, senior lecturer in reproduction and developmental medicine at the University of Sheffield, said: "I think this is a very exciting paper. We are still remarkably sketchy about some of the key molecules involved in the early stages of fertilisation when the sperm and egg first interact.
"Yet the information could be immensely useful to help in the diagnosis of infertility but also in the design of new novel contraceptives for both humans and other animal species.
"The identification of the Juno protein opens up many exciting prospects. Perhaps the most obvious biomedical application of this finding is whether screening for this protein (or its gene in a blood sample) could be used as a test of fertility.
"We know that fertilisation failure in IVF is quite rare, and so I suspect the lack or dysfunction of this protein is probably not a major cause of infertility in couples. However, it would be useful to know how many women have eggs that lack this protein so we can properly assess this.
"The second, and perhaps most likely application, is whether scientists could devise drugs or vaccines that could block the way this protein works or how the sperm protein Izumo1 interacts with it. This could lead to a new and novel non-hormonal contraceptive for both humans and other species of mammals."
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