A faulty gene could help explain some cases of unexplained male infertility, according to research.Mutations of the NR5A1 gene were found in a small percentage of infertile men, reports the American Journal of Human Genetics.Scientists from the Pasteur Institute in France and University College London said it could help doctors investigating men with the condition.
A UK expert said he hoped that further gene defects could be found.
In the majority of cases, doctors can find no cause for male infertility, despite it accounting for up to half of cases in which couples have difficulty conceiving.
Male infertility appears to be more common within certain families, and this leads scientists to believe that there may be a genetic root for some cases, but only a handful of gene mutations which might be responsible have actually been found.
The latest research looks at a gene already known to be involved in sexual development in both men and women - defects in NR5A1 have been linked to physical defects in the development of the testicles or ovaries.
Their findings suggest that, even where there is no physical evidence of a problem, defects in the gene may be hampering the ability to make sperm.
They looked at the gene in 315 apparently healthy men who had an unexplained inability to produce sperm.
From this group, they found mutations in the gene in just seven, and closer examination revealed the men had altered levels of sex hormones and, in one case, mild abnormalities in the cellular structure of the testicles.
The research authors, from the UCL Institute of Child Health in London and the Institut Pasteur in Paris, said: "We conclude that approximately 4% of men with otherwise unexplained failure to produce sperm carry mutations in the NR5A1 gene."
Although the find would affect only a small proportion of infertile men, other specialists believe that other similar discoveries could help build up a clearer picture of the origins of the condition.
Dr Allan Pacey, a senior lecturer in andrology at the University of Sheffield, said that there was still "embarrassingly little" known about the genetics behind male infertility.
"Given the complexity of the sperm production process it is likely that many genes are involved and therefore that may gene defects linked to infertility may be found.
"Although this gene defect affects only a small number of men, we need more studies like this so that we can fill in the gaps in our knowledge and possibly one day build a robust diagnostic test for male fertility based on genetics."
Scientists believe they have discovered a gene which plays a critical role in the development of sperm.
A Howard Hughes Medical Institute team found a defect in the Jhdma2a gene could cause some cases of infertility.The Nature study found mice lacking the gene were infertile, producing tiny numbers of abnormal sperm.
One of Britain's leading male fertility experts said that he was hopeful it could explain why some men cannot father children.
The reasons behind much male "sub-fertility" are not fully understood.
Some men who are unable to father a child naturally have abnormally shaped sperm, or very small numbers of sperm, and many research teams are hunting for genetic defects which might be responsible for this.
The Howard Hughes team believe their gene is vital for "spermiogenesis" which allows the DNA needed to create an embryo to be compacted into a tight ball inside the head of the sperm so that it can break through the outer surface of the egg.
To test whether Jhdma2a could affect sperm production, they bred mice without the gene.
These mice not only had unusually small testes, but had a very low sperm count, and could not produce offspring.
The few sperm that were produced by the mice had abnormally shaped heads and tails that could not move.
A closer look at these sperm using dyeing techniques under the microscope revealed that the DNA was not being packaged correctly in the head of the sperm.
Dr Yi Zhang, who led the project, said: "Defects in this gene could be the cause of some cases of male infertility.
"Because this gene has a very specific effect on the development of functional sperm, it holds great potential as a target for new infertility treatments that are unlikely to disrupt other functions within the body."
'Unique'
However, although the importance of the gene has been proven in mice, there is no certainty that it will play the same role in humans, and the team now plans to look at the DNA of infertile men to see if it is missing in any of them.
Dr Allan Pacey, a senior lecturer in andrology at the University of Sheffield, and Secretary of the British Fertility Society, said that the genes that controlled sperm development were poorly understood.
He said: "The way that sperm DNA is packaged into the sperm head is quite unique and we know even less about that.
"It would be very useful to translate this research into human males and see if it can explain why some men simply don't produce healthy sperm and are therefore sub-fertile."
by bbc
