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HONG KONG: In a discovery that offers new hope for infertile couples, researchers have figured out exactly how a human egg captures an incoming sperm to begin the fertilisation process.
The research identifies the sugar molecule called sialyl-LewisX (SLeX) that makes the outer coat of the egg 'sticky', which is vital for enabling the sperm and egg to bind together. Researchers across the world have been trying to understand what performs this task for over 30 years.
The scientists hope their work will help address some of the previously unexplained causes of human infertility and sub-fertility and be very useful for diagnosing this problem in couples who are unable to have children. It could also provide a new target for the development of natural contraceptive agents.
"This research provides an enlightening answer to a basic important question and human fertilisation - how does a sperm bind to an egg?" said co-author William Yeung from the University of Hong Kong (HKU) of the paper in the current issue of Science. "But this is only a first step that will lead to more discoveries."
Binding with sperm proteins
A sperm 'recognises' an egg when proteins on the head of the sperm meet and match a series of specific sugars in the egg's outer coat. Once a successful match has been made, the outside surfaces of the sperm and egg bind together before they merge and the sperm delivers its DNA to the inside, fertilising the egg.
The authors used ultra-sensitive mass-spectrometric imaging technology to assess which molecules were most likely to be key in the binding process. They discovered that SLeX is abundantly found on the egg's outer coat and that it is expressed at a much higher concentration than any of the other sugars that can be found on the thick transparent shell. From these results, they deduced that SLeX was most likely to be responsible for binding with proteins on the head of the sperm.
They tested whether SLeX was the key binding sugar using the outer coats of unfertilised and non-living human eggs, obtained by informed consent from in vitro-fertilisation patients. They carefully bisected the empty coat in a delicate procedure using a tiny knife, carried out under a powerful microscope.
Uncovering other molecules
The scientists treated one half with a chemical that prevented the SLeX sugar from binding, to see what effect this would have on a sperm's ability to bind to the egg. When they released sperm around the bisected egg, they found that significantly fewer bound to the treated half of the egg coat than the untreated half.
"Our knowledge on sperm-egg binding in humans is limited. The identification of SLeX would enable researchers to uncover other molecules involved in this important process of human life," said Yeung.
The World Health Organisation estimates that infertility affects up to 15% of reproductive-aged couples worldwide and almost one in every seven couples in Britain have problems conceiving a child for various clinical reasons, many of which are still unexplained by medical science. The researchers are now keen to use the findings of this study to further investigate the proteins on the head of a sperm that enable it to recognise an egg.
With the Imperial College London
