The reason it takes 200 million sperm to fertilise a single egg has been discovered and might lead to better fertility treatment.
A ‘secret handshake’ used by sperm to fertilise a woman’s egg has been identified by scientists.
The groundbreaking discovery could lead to improved IVF treatments and even better contraceptives.
Despite centuries of research we know little about what sperm do once inside a female.
This is because they are the only cells destined to be cast forth into a foreign environment.
The feat requires dramatic physical changes as they travel from the testes into a woman’s reproductive tract.
Now a US team has shed light on the phenomenon by showing cells lining the womb recognise sugar molecules, or glycans, on the surface of sperm.
Lead author Professor Pascal Gagneux, a molecular anthropologist at the University of California, San Diego, said: “It has the makings of a ‘secret handshake’ between sperm and the cells lining the uterus.”
The study published in the Journal of Biological Chemistry reveals for the first time how sperm behave within female bodies – an area still in its relative infancy.
It offers hope of finding a way to select the healthiest sperm during assisted reproduction.
In natural conception up to 250 million sperm fight their way through the woman’s reproductive canal to be whittled down to a handful. Eventually, only one reaches the egg.
But in IVF the egg is placed in a solution with millions of sperm, or else a lab technician selects just one with which to fertilise an egg.
When the sperm arrive in the womb they face a bombardment by the immune system. Many may be needed so some will survive or there may be a benefit to the cull.
Prof Gagneux said: ” For an egg, being too easy to fertilise is bad; being too difficult to fertilise is also bad.”
His lab experiments found uterine cells express a receptor that sticks to the sugary chemicals – helping them to decide on the strongest one.
Prof Gagneux and colleagues describe this interaction as a “handshake”. They believe it adjusts the female’s immune response so some make it through to the fallopian tubes.
Sperm are foreign to a woman and treated as unwanted invaders. White blood cells kill them all bar one – the strongest individual. But her response, called the ‘leukocytic reaction’, remains a mystery.
Explained Prof Gagneux: “What we do know is after crossing the cervix, millions of sperm – about the size of the US population – that arrive in the uterus are faced by a barrage of macrophages and neutrophils.”
This attack by the innate immune system reduces hundreds of millions of the sperm in semen down to just a few hundred that enter the fallopian tubes.
The reason may be to prevent an egg being fertilised by more than one sperm, meaning it cannot develop, a condition called polyspermy.
Sperm are coated in glycans that are rich in sialic acid which the immune system uses to differentiate human cells from invaders.
The researchers initially expected them to communicate with immune cells called neutrophils.
But tests on the latter did not seem to make much difference between sperm with and without sialic acid.
Meanwhile, they observed sialic acid binding receptors called siglecs on endometrial cells that line the womb. In solution, these can bind to whole sperm.
The binding interaction may help the sperm run this gantlet – for example, by dampening the immune response, said Prof Gagneux.
Alternatively, it may be a way for uterine cells to weed out faulty sperm. In the immune system, this receptor class helps cells to recognise sialic acid molecules as ‘its own’, so they can turn inflammation either up or down.
Prof Gagneux said: “It is somewhat embarrassing how little we can say about what this interaction means.”
The first step in understanding its physiological significance will be to look for direct interaction between sperm and intact uterine tissue.
Added Prof Gagneux: “In some ways, it is humbling to be working in such a poorly understood area.
“Reproduction is a very, very delicate tug-of-war at many levels. The fact there is (also) this immune game going on is completely fascinating.”
In the UK more than 20,000 babies a year are born through IVF since Oldham’s Louise Brown became the first in 1978.
Biologists first looked upon sperm cells in their full glory in the 17th century, using the world’s first microscope. Their full life cycle has stayed largely under wraps ever since.