Scientists have identified a protein essential for human sperm to fuse to an egg, which could lead to new methods of treating infertility.
Sperm's journey to the egg is not simple
The Japanese team has named the protein Izumo, after a Japanese shrine dedicated to marriage.
In laboratory tests mouse sperm which did not have the protein were unable to fuse with the egg.
Writing in Nature, the team suggest the discovery could also lead to new methods of contraceptives.
Sperm has a number of barriers to get through in its Indiana Jones type quest for the 'Holy Grail' of fertilising the egg.
First, it must pass through a barrier of follicle cells surrounding the freshly ovulated egg.
Next, it has to penetrate the egg's outer wall, the zona pellucida, a thick layer that protects the egg, so that it can bind to the plasma membrane beyond it.
In the Japanese study, carried out at Osaka University, male mice who were genetically engineered to lack the Izumo protein were found to be infertile.
The sperm from the mice was able to penetrate both of the barriers around the egg, but not a single Izumo-deficient sperm was seen to fuse with the egg membrane.
The team has discovered that a form of the Izumo protein also exists on human sperm.
Tests showed that an antibody designed to react against the protein blocked the fusion of human sperm with hamster eggs, which is a recognised test for male fertility.
Writing in Nature, the team led by Dr Masaru Okabe, said: "Our finding not only provides insight into the enigmatic fusion mechanism [of the egg and the sperm], but also promises benefits in the clinical treatment of infertility and the potential development of new contraceptive strategies."
In the same journal, Dr Richard Schultz and Dr Carmen Williams of the Center for Research on Reproduction and Women's Health at the University of Pennsylvania, said the findings raised the possibility the protein could be the source of "new targets for non-hormonal contraception".
Dr Simon Fishel, fertility expert and director of Care Fertility, told the BBC News website: "This is a fascinating and tantalising study.
"They are identifying the actual sperm molecule involved in fusing with the egg - and that begins the whole process.
"The finding offers a whole number of possibilities for contraception, potentially reversible ways of providing non-hormonal methods, as opposed to sterilisation.
"It is enormously exciting"
Dr Fishel said the study could also offer an reason for some of the couples affected by 'unexplained infertility'.
And he said that if the man's sperm did lack the Izumo protein, it would mean doctors would know they had to inject sperm directly into the egg to trigger fertilisation.