Mutated gene tied to infertility

UCL (UK) — A genetic trait previously linked to female infertility is now also linked to some cases of male infertility.

One in seven couples worldwide has difficulty conceiving a child, and male infertility is thought to account for nearly half of those cases.

Although the cause of male infertility is often unknown, a genetic alteration that disrupts sperm production in otherwise healthy men may offer new insight.

John Achermann, a Wellcome Trust Senior Fellow from the Institute of Child Health at University College London (UCL) and Ken McElreavey and Anu Bashamboo from the Pasteur Institute in France examined whether the NR5A1 gene might be involved in some cases of male infertility.

Details are published in the American Journal of Human Genetics.

“Many genes are known to be essential for the production of sperm, but there are surprisingly few single gene changes that have been conclusively demonstrated to cause a failure of sperm production in humans,” the study says.

The NR5A1 gene codes for a key protein called steroidogenic factor 1 that regulates fetal, prepubertal, and adult sex development.

Previous work had shown that NR5A1 mutations are associated with severe defects in the development of the testes or ovaries as well as significant anomalies of the male external genitalia.

The researchers identified seven men with severe failure to produce sperm who carried changes in the NR5A1 gene and showed that the mutations impaired the ability of the steroidogenic factor 1 protein to regulate the transcription of key reproductive genes.

The mutations were associated with altered levels of sex hormones and, in the one case studied, mild abnormalities in the cellular structure of the testes. Similar genetic alterations were not observed in more than 2,000 control samples.

These findings suggest that changes in NR5A1 are not just associated with severe and obvious defects in reproductive development.

The authors conclude that approximately four percent of men with otherwise unexplained failure to produce sperm carry mutations in the NR5A1 gene.

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