The secret life of sperm is unlocked

Infertile couples may be spared years of fruitless treatment with the discovery that the human egg can read the father's genetic key and screen out failures

Thousands of infertile couples could be spared the pain, anguish and expense of fruitless IVF treatments, thanks to the discovery of a lock-and-key mechanism between sperm and egg cells.

The research could explain why so many couples with no apparent reproductive problems are unable to conceive. Although more than 40,000 in vitro fertilisation cycles are prescribed in Britain each year, only 10,000 births result.

In addition to the £5,000 cost of each cycle, the couples face huge amounts of stress and can suffer severe depression and in some cases divorce. "Our work has quite a lot of relevance for humans and society and one of the main ones is infertility," said Dr Martin Brinkworth, a member of the team at the universities of Bradford and Leeds that discovered the lock-and-key mechanism.

Some 15 per cent of couples have trouble conceiving, about half of them because the man has a problem. But in only one third of cases is the cause obvious, such as a low sperm count, malformation or poor swimming ability. This leaves 2 per cent of the male population, about 330,000 adult men in the UK (not all of whom will be trying to have children), who are infertile for no discernable reason.

Dr David Miller at the University of Leeds thinks the secret could be that the genetic keys in their sperm don't quite fit their partners' locks. "Our research offers a plausible explanation for why some sperm malfunction," he said.

His colleague Dr David Iles added: "There is a definite pattern to the way DNA is packaged in sperm cells. It is the same in unrelated fertile men, but it is different in the sperm of infertile men."

If a test could be developed to identify these men, up to a quarter of women who have intrusive fertility checks would be spared the procedures. It could also sharply decrease the 75 per cent failure rate of IVF by filtering out male candidates who have no chance of success. Private patients and the NHS could save as much as £50m a year if all cases of male infertility were identified in advance.

The Leeds-Bradford research, and parallel work by a US team at the University of Utah, fundamentally changes our understanding of the importance sperm has in the developing embryo.

Although the egg and sperm each supply half the DNA for the new baby, the egg provides all the cellular support systems, including enzymes and proteins. Until now, it was thought that sperm simply delivered the father's tightly packed DNA to the egg, leaving control and regulation of the process to the mother's DNA.

But the two teams of scientists, have found that some genes are left exposed in sperm, in an "open conformation", allowing them to play an important role in the development of the embryo. "It contradicts the dogma that the egg does everything," said Dr Brinkworth, a senior lecturer at the University of Bradford.

The British team has also identified how these "open" areas are formed and evidence that they can be read by the egg, suggesting that they act as a signature or key, revealing the species the sperm comes from and signalling whether the DNA is in good shape.

Although no clinical test is available now, the researchers are hopeful that one can be developed after they've identified all the DNA bases in the open areas, some of which might be usable as markers.

The molecule at the heart of the lock-and-key mechanism is a protein called CTCF, say the scientists in a paper published in the journal Genome Research. "CTCF sets the stage during sperm development," said Dr Iles. "And open bases can be recognised by CTCF in the egg."

If stretched out end to end, the DNA from a single human cell would be about 1.8m long. But in the cell nucleus, it is wrapped around molecules called histones, which link up to form an efficient three-dimensional scaffold, 40,000 times shorter than the unfolded DNA. Histones also play a role in turning genes on so that their coded instructions can be copied and sent to other parts of the cell.

But sperm don't have elaborate cells, just a tightly packed nucleus and a tail for swimming to the egg. So when they form, the histones are stripped off and replaced with another molecule called protamine, which shapes the DNA into an even tighter bundle, where the genes cannot be read.

The British researchers have found, however, that CTCF protects some histones in sperm from being replaced, leaving about 4 per cent of the genome in an open conformation, so that its instructions can be copied. Since the pattern of exposed areas is not random, they believe it must have a purpose, and the simplest explanation is that it is a key that influences the developing embryo even before the father's genetic contribution has been unpacked.

The discovery has implications for research in fields other than human reproduction. Although the bulk of their work involved 50 million human sperm cells from several donors, the Bradford-Leeds team also found similar structures in mouse sperm.

The lock-and-key mechanism could help to explain how closely related species maintain their separate identities, even when individual members have sex. "DNA from different organisms can be extremely similar," said Dr Iles. "Why do they not produce offspring, or if they do, why is it sterile, like mules and donkeys?"

The team speculates that this may have been the fate of prehistoric couplings between humans and their close cousins, Neanderthals, with incompatible keys and locks ensuring that any offspring would be unable to breed.

This would explain why the human genome has no trace of Neanderthal DNA despite the two similar species living close together for millennia.

The misery of unexplained infertility

Susan Seenan is deputy chief executive of the Infertility Network UK

About a third of the couples we speak to suffer from unexplained infertility, which can often be harder to deal with. I think men find it particularly difficult if they find out they're infertile. In general men find it very hard to talk about infertility and there's a stigma attached; some still see it as a slight on their manhood if they can't have a child.

At least with a low sperm count or blocked fallopian tubes a couple can try to find a solution and they know what they're dealing with. But when it's unexplained it's stressful.

It can be difficult for other people to understand what's wrong with you; the longer time that goes by without conceiving, the more stressed you get. When it's unexplained there's always a hope that it might happen naturally, so the emotional impact of the disappointment every month when you haven't conceived is really tough. At least if you know what's wrong you know where you stand.

If you have a proven cause of infertility then you can be eligible for NHS treatment, but those whose infertility is unexplained have to wait for three years. That can be a long time when you're older and time is not on your side.

www.infertilitynetworkuk.com

News
Russell Brand was in typically combative form during his promotional interview with Newsnight's Evan Davis
peopleReports that Brand could stand for Mayor on an 'anti-politics' ticket
News
The clocks go forward an hour at 1am on Sunday 30 March
news
Arts and Entertainment
The Doctor finds himself in a forest version of London in Doctor Who episode 'In the Forest of the Night'
TVReview: Is the Doctor ever going stop frowning? Apparently not.
News
Voluminous silk drawers were worn by Queen Victoria
newsThe silk underwear is part of a growing trade in celebrity smalls
PROMOTED VIDEO
Life and Style
ebooksA superb mix of recipes serving up the freshest of local produce in a delicious range of styles
Life and Style
ebooksFrom the lifespan of a slug to the distance to the Sun: answers to 500 questions from readers
Sport
footballMatch report: Real fight back to ruin Argentinian's debut
News
Candidates with surnames that start with an A have an electoral advantage
newsVoters are biased towards names with letters near start of alphabet
Arts and Entertainment
Isis with Lord Grantham (Hugh Bonneville)
TV
Arts and Entertainment
Jay James
TVReview: Performances were stale and cheesier than a chunk of Blue Stilton left out for a month
Latest stories from i100
Have you tried new the Independent Digital Edition apps?

ES Rentals

    Independent Dating
    and  

    By clicking 'Search' you
    are agreeing to our
    Terms of Use.

    iJobs Job Widget
    iJobs General

    Maths Teacher

    £110 - £200 per day: Randstad Education Leeds: Secondary Maths Teacher for spe...

    Business Analyst - Surrey - Permanent - Up to £50k DOE

    £40000 - £50000 Per Annum Excellent benefits: Clearwater People Solutions Ltd:...

    ***ASP.NET Developer - Cheshire - £35k - Permanent***

    £30000 - £35000 Per Annum Excellent benefits: Clearwater People Solutions Ltd:...

    ***Solutions Architect*** - Brighton - £40k - Permanent

    £35000 - £40000 Per Annum Excellent benefits: Clearwater People Solutions Ltd:...

    Day In a Page

    Wilko Johnson, now the bad news: musician splits with manager after police investigate assault claims

    Wilko Johnson, now the bad news

    Former Dr Feelgood splits with manager after police investigate assault claims
    Mark Udall: The Democrat Senator with a fight on his hands ahead of the US midterm elections

    Mark Udall: The Democrat Senator with a fight on his hands

    The Senator for Colorado is for gay rights, for abortion rights – and in the Republicans’ sights as they threaten to take control of the Senate next month
    New discoveries show more contact between far-flung prehistoric humans than had been thought

    New discoveries show more contact between far-flung prehistoric humans than had been thought

    Evidence found of contact between Easter Islanders and South America
    Cerys Matthews reveals how her uncle taped 150 interviews for a biography of Dylan Thomas

    Cerys Matthews on Dylan Thomas

    The singer reveals how her uncle taped 150 interviews for a biography of the famous Welsh poet
    DIY is not fun and we've finally realised this as a nation

    Homebase closures: 'DIY is not fun'

    Homebase has announced the closure of one in four of its stores. Nick Harding, who never did know his awl from his elbow, is glad to see the back of DIY
    The Battle of the Five Armies: Air New Zealand releases new Hobbit-inspired in-flight video

    Air New Zealand's wizard in-flight video

    The airline has released a new Hobbit-inspired clip dubbed "The most epic safety video ever made"
    Pumpkin spice is the flavour of the month - but can you stomach the sweetness?

    Pumpkin spice is the flavour of the month

    The combination of cinnamon, clove, nutmeg (and no actual pumpkin), now flavours everything from lattes to cream cheese in the US
    11 best sonic skincare brushes

    11 best sonic skincare brushes

    Forget the flannel - take skincare to the next level by using your favourite cleanser with a sonic facial brush
    Paul Scholes column: I'm not worried about Manchester United's defence - Chelsea test can be the making of Phil Jones and Marcos Rojo

    Paul Scholes column

    I'm not worried about Manchester United's defence - Chelsea test can be the making of Jones and Rojo
    Frank Warren: Boxing has its problems but in all my time I've never seen a crooked fight

    Frank Warren: Boxing has its problems but in all my time I've never seen a crooked fight

    While other sports are stalked by corruption, we are an easy target for the critics
    Jamie Roberts exclusive interview: 'I'm a man of my word – I'll stay in Paris'

    Jamie Roberts: 'I'm a man of my word – I'll stay in Paris'

    Wales centre says he’s not coming home but is looking to establish himself at Racing Métro
    How could three tourists have been battered within an inch of their lives by a burglar in a plush London hotel?

    A crime that reveals London's dark heart

    How could three tourists have been battered within an inch of their lives by a burglar in a plush London hotel?