Gene Mutation Linked to Male Infertility

Amber Angelle

Date: 30 September 2010 Time: 12:26 PM ET

As increasing numbers of couples are seeking reproductive assistance, scientists are searching for a genetic explanation of infertility in otherwise healthy men and women.

In the case of male infertility, new research published online today (Sept. 30) in the American Journal of Human Genetics offers some answers. Mutations in a single gene can cause an abnormally low sperm count in some men, according to a team of researchers led by Amu Bashamboo at the Pasteur Institute in Paris.

The gene, called NR5A1, has been known to be associated with severe disorders of the reproductive system, such as abnormal development of the testes. Last year, Bashamboo and others linked mutations in NR5A1 with ovarian dysfunction in women. In their study published in The New England Journal of Medicine, they wrote that women who inherited particular mutations of the gene suffered from a "progressive loss of reproductive capacity."

"When we found this association in women," Bashamboo said, "we considered it likely that NR5A1 mutations may also be associated with male infertility."

In their new study, the researchers analyzed the DNA of 315 men who were diagnosed with infertility of an unknown cause (in most cases of male infertility, the cause is unknown). They found that seven of the men had mutations in NR5A1.

They then scanned DNA samples from 2,000 fertile men, and found no evidence of the mutations.

"Mutations in NR5A1 have always been associated with anomalies of gonad development," Bashamboo said, "but usually they were severe."

Because two of the men with the mutations were in their late 30s and early 40s, and another man showed a decline in sperm count over a two-year period, the researchers hypothesize that the mutations may cause a hastened decline in fertility with age.

In other words, a man with the mutation may have no trouble with his fertility when he's 21, but if he tries to have children later, it may no longer be possible.

How these mutations affect sperm count still requires further study, the researchers said. Some sperm may never fully develop, or sperm production may be low due to decreased levels of testosterone.

Another possibility, the researchers said, is that chemicals in the environment may alter the gene. In the last several years, studies by researchers in Japan and the United States have shown that the chemical atrazine, which is commonly used as an herbicide, disrupts the normal function of NR5A1 in fish and humans, demasculinizes animals, and increases the risk of reproductive cancer in animals and humans.

But many of those findings are preliminary, and they require larger studies in humans, the researchers said.

"The central theme is to better understand the development and function of the mammalian gonad," Bashamboo told My Health News Daily. "So we continue to look for novel genetic causes to understand the pathophysiology of male and female infertility, while at the same time researching the anomalies we've already found."

This article was provided by MyHealthNewsDaily, a sister site to LiveScience.