3 July 2015
A new study has identified a gene, which researchers believe could be one of the main causes of male infertility. In the most severe form, men do not make measurable levels of sperm. This condition - azoospermia - affects one per cent of the male population but the underlying cause is often unknown.
Led by a team at University of Pennsylvania, a new study suggests that mutations in the X chromosome gene called TEX11 are responsible for a significant number of cases of infertility, around one per cent of non-obstructive azoospermia.
The study, published in the journal EMBO Molecular Medicine, is based on research conducted in 2008, which found that disrupting Tex11 function caused sterility in male mice and caused female mice to have smaller litters.
This is because the disruption halts the maturation of germ cells by interfering with meiosis, which divides genetic material that is then sorted into what eventually becomes eggs and sperm.
Dr Jeremy Wang, a professor in the Department of Biomedical Sciences at Penn's School of Veterinary Medicine and senior author of the study, looked at genomic samples from 246 men with azoospermia, as well as a control group. They found more variants in men with azoospermia than in the controls, suggesting that the protein plays a key role in sperm development.
The researchers found a person carrying a mutation in the TEX11 gene who had an interesting family history. Both he and his brother were azoospermic, and a genetic sample taken from his mother showed that she was heterozygous for the TEX11 mutation. Their investigation suggested that the condition could be passed down the maternal line on the X chromosome.
To experimentally test whether the mutations that were identified in infertile men were the reason for their azoospermia, the team selected three mutations found in the azoospermic men that were not present in the control group.
They engineered mice with versions of Tex11 that had the same mutations and experimentally bred mice to express those mutated versions. Two of these mutations saw little effect but the third had a significant impact.
The team found males with this variant had significantly lower sperm counts than control animals. Researchers found three mutations in TEX11 that appeared to be the cause of the infertility, resulting in a rate of about one per cent of cases of azoospermia.
"Given that there are hundreds of candidate genes for male infertility," Dr Wang said, "One per cent is actually very significant."
The findings could have major implications for genetic counseling for infertility.
"If men had one of these same mutations in this gene, I think we could safely say that's the cause of their infertility," Dr Wang said.
Posted by Edward Bartel
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