Laygo, Demi Jamie

BIO1
2014-48931
WFW

Fertility mystery solved: protein discovered that joins

sperm with eggs
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 Wellcome Trust
Sanger Institute in Hinxton, Cambridgeshire.
"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."
http://www.theguardian.com/science/2014/apr/16/fertility-mystery-solved-
protein-discovered-joins-sperm-eggs