The secret life of sperm is unlocked - Health News - Health & Families - The Independent

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
Paper trail: the wedding photograph found in the rubble after 9/11 – it took Elizabeth Keefe 13 years to find the people in it
newsWho are the people in this photo? It took Elizabeth Stringer Keefe 13 years to find out
Arts and Entertainment
Evil eye: Douglas Adams in 'mad genius' pose
booksNew biography sheds light on comic genius of Douglas Adams
Sport
FootballFull debuts don't come much more stylish than those on show here
News
i100
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
Life and Style
Kim Kardashian drawn backlash over her sexy swimsuit selfie, called 'disgusting' and 'nasty'
fashionCritics say magazine only pays attention to fashion trends among rich, white women
Arts and Entertainment
TVShows like Agents of S.H.I.E.L.D are little more than marketing tools
Arts and Entertainment
Hit the roof: hot-tub cinema east London
architectureFrom pools to football pitches, rooftop living is looking up
Travel
travel
News
The ecological reconstruction of Ikrandraco avatar is shown in this illustration courtesy of Chuang Zhao. Scientists on September 11, 2014 announced the discovery of fossils in China of a type of flying reptile called a pterosaur that lived 120 millions years ago and so closely resembled those creatures from the 2009 film, Avatar that they named it after them.
SCIENCE
Life and Style
tech
Arts and Entertainment
Matisse: The Cut-Outs exhibition attracted 562,000 visitors to the Tate Modern from April to September
art
Life and Style
Models walk the runway at the Tom Ford show during London Fashion Week Spring Summer 2015
fashionLondon Fashion Week 2014
News
Kenny G
news
News
peopleThe black actress has claimed police mistook her for a prostitute when she kissed her white husband
Life and Style
techIndian model comes with cricket scores baked in
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

    Primary Teacher

    £110 - £150 per day: Randstad Education Newcastle: Our clients are looking for...

    KS1 and KS2 Primary NQT Job in Lancaster Area

    £85 - £140 per day: Randstad Education Preston: Randstad Education is urgently...

    Supply teachers needed- Worthing!

    £100 - £120 per day: Randstad Education Crawley: Supply teachers needed for va...

    KS1 and KS2 Primary NQT Job in Lancaster Area

    £85 - £140 per day: Randstad Education Preston: Randstad Education is urgently...

    Day In a Page

    Mystery of the Ground Zero wedding photo

    A shot in the dark

    Mystery of the wedding photo from Ground Zero
    His life, the universe and everything

    His life, the universe and everything

    New biography sheds light on comic genius of Douglas Adams
    Save us from small screen superheroes

    Save us from small screen superheroes

    Shows like Agents of S.H.I.E.L.D are little more than marketing tools
    Reach for the skies

    Reach for the skies

    From pools to football pitches, rooftop living is looking up
    These are the 12 best hotel spas in the UK

    12 best hotel spas in the UK

    Some hotels go all out on facilities; others stand out for the sheer quality of treatments
    These Iranian-controlled Shia militias used to specialise in killing American soldiers. Now they are fighting Isis, backed up by US airstrikes

    Widespread fear of Isis is producing strange bedfellows

    Iranian-controlled Shia militias that used to kill American soldiers are now fighting Isis, helped by US airstrikes
    Topshop goes part Athena poster, part last spring Prada

    Topshop goes part Athena poster, part last spring Prada

    Shoppers don't come to Topshop for the unique
    How to make a Lego masterpiece

    How to make a Lego masterpiece

    Toy breaks out of the nursery and heads for the gallery
    Meet the ‘Endies’ – city dwellers who are too poor to have fun

    Meet the ‘Endies’ – city dwellers who are too poor to have fun

    Urbanites are cursed with an acronym pointing to Employed but No Disposable Income or Savings
    Paisley’s decision to make peace with IRA enemies might remind the Arabs of Sadat

    Ian Paisley’s decision to make peace with his IRA enemies

    His Save Ulster from Sodomy campaign would surely have been supported by many a Sunni imam
    'She was a singer, a superstar, an addict, but to me, her mother, she is simply Amy'

    'She was a singer, a superstar, an addict, but to me, her mother, she is simply Amy'

    Exclusive extract from Janis Winehouse's poignant new memoir
    Is this the role to win Cumberbatch an Oscar?

    Is this the role to win Cumberbatch an Oscar?

    The Imitation Game, film review
    England and Roy Hodgson take a joint step towards redemption in Basel

    England and Hodgson take a joint step towards redemption

    Welbeck double puts England on the road to Euro 2016
    Relatives fight over Vivian Maier’s rare photos

    Relatives fight over Vivian Maier’s rare photos

    Pictures removed from public view as courts decide ownership
    ‘Fashion has to be fun. It’s a big business, not a cure for cancer’

    ‘Fashion has to be fun. It’s a big business, not a cure for cancer’

    Donatella Versace at New York Fashion Week