Gene Mutation May Be Linked to Male Infertility

Study May Lead to New Ways of Treating Infertility in Men

By Salynn Boyles
WebMD Health News

Reviewed by Laura J. Martin, MD

July 20, 2011 -- Researchers say they have discovered a genetic mutation that may explain a significant proportion of male infertility.

The finding could potentially improve current testing, which still fails to find a cause for infertility in about one in five couples. And it could lead to earlier treatment of these couples.

Researchers at the University of California, Davis made the discovery during an unsuccessful attempt to develop a contraceptive vaccine using a germ-killing protein found on mucus surfaces, known as DEFB126.

The sperm-coating protein is produced in the epididymis, which is where sperm are stored after being produced in the testes. The protein helps the sperm penetrate a woman's cervical mucus to reach the egg for fertilization.

While cloning the gene for study in their lab, the researchers detected the genetic mutation that keeps DEFB126 from performing this function. Further study revealed that the mutation is very common.

"This gratuitous discovery is the type that makes a scientist almost giddy with excitement," University of California, Davis professor of immunology Charles L. Bevins, MD, PhD, said at a news conference today. "But it also raised concern because in laboratory science often what seems too good to be true, actually is."

The researchers were able to show that the mutation lowers fertility by studying 500 newly married couples in China.

An analysis of the research is published Science Translational Medicine.

Seeking Causes of Infertility

Between 10% and 15% of couples at some point experience infertility, which is defined as the inability to conceive after a year of unprotected sex.

About half of infertility cases are believed to involve the male partner, but no obvious cause is identified in about 70% of infertile males, says study co-researcher Theodore Tollner, MD.

When the researchers examined sperm samples from the U.S., U.K., and China, they found that about one in four of the samples carried two copies of the defective gene, which could potentially affect fertility.

Tollner says sperm samples from men with the gene mutation usually appeared normal with regard to measures such as sperm count, sperm shape, and swimming strength.

"These fertility values were about the same for men in our study, regardless of whether they possessed the normal or mutated gene," he says. "So looking at these sperm in conventional ways -- which is the way men would be evaluated in fertility clinics -- you would have no reason to think that many of the men with the genetic mutation would have reduced sperm function and a potential problem with fertility."

Tollner says identifying men with the mutation may prove to be a better indicator of male infertility than currently used measures.

Identifying Men With Genetic Mutation

The group's effort to confirm that the mutation contributes to infertility took them to Anhui, China.

A team led by Scott Venners and colleagues from British Columbia's Simon Fraser University examined the sperm of 500 newly married men whose wives were trying to conceive, and they then followed the couples for almost two years.

The birth rate among couples in which the man carried two copies of the defective DEFB126 gene was found to be 30% lower than the other couples in the study.

Study co-researcher Gary Cherr, PhD, of the University of California, Davis, says once the clinical significance of the finding is confirmed, identifying men with the double mutation should not be difficult. He says an at-home test kit could be developed to help couples avoid expensive clinical testing.

In an editorial published with the study, gene researcher Steve Rosen, PhD, of Duke NUS Medical School in Singapore, writes that it is too soon to predict how the mutation's discovery will affect infertility screening and treatment.

"It is clear that this genetic information could lead to more informed assisted reproduction in addition to possible new methods of treating sperm," he writes. "In the meantime, we eagerly await a more complete understanding of the epidemiology of the DEFB126 [mutation] and of the mechanisms by which it increases time to pregnancy."


Men and women are equally likely to have fertility problems. See Answer

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SOURCES: Tollner, T.L. Science Translational Medicine, July 20, 2011; vol 3.Theodore Tollner, MD, department of obstetrics and gynecology, University of California, Davis.Gary Cherr, PhD, departments of environmental toxicology and nutrition, Bodega Marine Laboratory, University of California, Davis.Charles Bevins, MD, PhD, department of medical microbiology and immunology, University of California, Davis.Scott Venners, PhD, assistant professor of epidemiology, Simon Fraser University, British Columbia, Canada. ©2011 WebMD, LLC. All Rights Reserved.