Every human life begins with the union between an egg and a sperm. We wouldn’t exist without this intimate connection, but its details are still shrouded in mystery. Which molecules, for example, bind the two cells together? Poh-Choo Pang from Imperial College and Philip Chiu from the University of Hong Kong have started to answer this question. Earlier this year, they announced that they had discovered the molecule on the surface of the egg that captures an incoming sperm.
In 1982, scientists showed that the sperm recognises large sugar molecules on the egg’s outer coat because competing sugars can interfere with this interaction. But in the 30 years since, no one has managed to identify the specific molecule, partly because human eggs are difficult to come by and they’re tiny. Pang and Chu got round that problem by analysing 195 unfertilised eggs, obtained by informed consent from IVF patients.
Using mass spectrometry, they showed that the outer coat of the eggs – the zona pellucida – is studded with large sugars called sialyl-LewisX or SLeX. This one molecule makes up more than 99% of the carbohydrates on the surface of the egg, even though it’s fairly rare on other cells.
Pang and Chiu reasoned that SLeX is the hitching post that the sperm hooks up to. To prove that, they cut human eggs into two halves, and treated one of them with an antibody that blocks SLeX. This simple act cloaked the egg, which lost its hold upon incoming sperm. The other half, whose SLeX molecules were still unveiled, attracted sperm normally. Pang and Chiu also attached a glowing label onto SLeX to show that it does indeed stick to sperm.
SLeX was previously associated with cancer and sepsis – diseases that claim millions of lives. But Pang and Chiu have shown that SLeX is also there at the start of every life, bringing sperm and eggs together.
It is difficult to underscore the significance of this finding,
say Alexander Pastuszak and Dolores Lamb from Baylor College of Medicine, who recently evaluated the paper. The discovery is one half of the puzzle. We still don’t know the molecule on the sperm that SLeX interacts with, but we now have better odds of finding it.
Pastuszak and Lamb also say,
[That] will result in another very significant contribution to understanding the fundamental science and beauty of… fertilization in humans.
This could tell us more about why some people are infertile, or even point the way to new contraceptive chemicals.