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."
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."