The Howard Hughes team noted that mice lacking the Jhdma2a gene were infertile and only produce tiny numbers of abnormal sperm. One of Britain's leading male fertility experts expressed high hopes that the discovery could lead to some answers as to why there are some men who are incapable of fathering a child. Much of the reasons behind male “sub-fertility” remains vague to be fully understood.
Abnormally-shaped sperm or very low sperm count are two of the reasons why some men are not able to father a child. Many research studies are looking at genetic defects to be responsible for these conditions. The team of experts from Howard Hughes believed that the Jhdma2a gene is crucial 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. Spermiogenesis is the final maturation stage of sperm, when the cell builds its pseudopod, acquires the ability to crawl, and becomes capable of fertilizing an oocyte.
In order to find out if Jhdma2a gene could affect sperm production, they experimented on mice and bred these animals without the Jhdma2a gene. These mice turned out to have unusually small testes, had a very small number of sperm production, and could not produce offspring. They even noted that not only do these mice have unusually small testes, but the small number of sperm they produced had abnormally-shaped heads and tails that were found to be immobile. When the sperm was examined using dyeing techniques under a microscope, it revealed that the DNA was not being packaged correctly in the head of the sperm.
“Defects in this gene could be the cause of some cases of male infertility,” said Dr. Yi Zhang, project leader of the Howard Hughes team. “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,” he said.
Although the significance of the Jhdma2a gene has already been proven in mice, there is no certainty that it will have the same effect in humans. The next big step for the team is to focus on the DNA of infertile men to see if it is missing in any of them.
According to Dr. Allan Pacey, a senior lecturer in Andrology at the University of Sheffield and Secretary of the British Fertility Society, the genes that controlled sperm development were poorly understood. “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,” he said.
