Severe spermatogenic failure (SSF) is a genetic condition that causes low sperm count and infertility. New insights into the genetic alterations that cause this disorder and their prevalence in populations of men around the world are provided by a study published by Cell Press in the American Journal of Human Genetics on October 25. The findings reveal which alterations are the greatest risk factors for the disease, and they could be immediately applicable in genetic counseling for assisted reproduction.

“Medically relevant population genetics studies are well established for most of the human genome, but this is the first study of this kind for the Y chromosome,” says study author Steve Rozen of Duke-National University of Singapore Graduate Medical School. “This study let us determine for the first time that two types of deletions jointly account for 8% of severely low sperm count.”

The most common known genetic causes of SSF are deletions in the Y chromosome’s AZFc region. Six deletions in this region have been reported, but it was not known how prevalent they are in the general population or how much they increase the risk of the disorder. To answer these questions, Rozen and his collaborators screened for these six deletions in more than 20,000 men from India, Poland, Tunisia, Vietnam, and the United States.

The team detected four of the six previously described deletions, whose prevalence varied dramatically across populations, and identified one of these deletions as a strong risk factor for SSF. The most common deletion - known as gr/gr - was found in about 2% of men as well as 2% of cases and almost doubled the risk of SSF. More notably, the rare b2/b4 deletion, found in well under 1% of men, increased the risk of SSF by a factor of 145 and accounted for about 6% of cases.

“Our study reveals that these two deletions are largely responsible for the AZFc region’s contribution to SSF,” Rozen says. “The immediate clinical use of these findings would be in genetic counseling, especially when a man with one of these deletions is using assisted reproduction to have a child.”

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Rozen et al.: “AZFc Deletions and Spermatogenic Failure: A Population-Based Survey of 20,000 Y Chromosomes.”

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Elisabeth (Lisa) Lyons
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Cell Press