Defect in Sperm Cloaking Protein May Explain Male Infertility

Infertile men may have a gene defect that takes away a protein that cloaks and protects sperm against a woman’s immune system while traveling to the egg, according to a study that offers a new explanation for some male infertility.

Although the sperm from men with the gene variant look normal under a microscope, they are less able to move through a solution made to resemble human cervical mucus, researchers reported today in Science Translational Medicine. When the cloaking protein was added to the sperm, they regained their swimming abilities, the study found.

About 10 percent of women of childbearing age have difficulty getting pregnant, and one in three cases involves male infertility, according to the National Institutes of Health. In another third of cases, the cause of infertility isn’t known. The discovery announced today may aid in those cases, the authors of the study wrote.

“This is the kind of discovery that makes scientists almost giddy with excitement,” said Charles Bevins, the study author and a microbiologist at the University of California, Davis, said today during a conference call.

When scientists tried to clone the cloaking protein from the sperm in lab studies, they noticed the mutation, Bevins said. The mutation was so significant that no protein was made. Also, it was a gene involved in reproductive success, where mutations usually aren’t seen.

Earlier Treatment

In about 70 percent of infertile men, the sperm count and quality don’t explain the infertility, said Gary Cherr, the paper’s senior author and a professor at the University of California, Davis. Knowing the cause of infertility may lead to earlier treatment, allowing patients to bypass expensive testing.

“We envision a clinical or home kit for detecting the presence or absence” of the gene, Cherr said.

About 50 percent of men worldwide carry one defective copy of the gene, called DEFB126, according to the report. These men can still form normal sperm. Another 25 percent carry two defective copies and produce sperm that are poor at swimming through mucus.

By diagnosing the problem early, doctors can avoid certain tests and switch to a fertility treatment that involves directly implanting the sperm into an egg.

In a study cited by the report, 500 couples in China showed that birth rates were 30 percent lower among those in which the husband had two copies of the gene than among those with men who had one or no mutations.

“The mutated gene reduced the rate of contraception, so it took them longer to achieve a pregnancy,” said Scott Venners, another study author, and epidemiologist at Simon Fraser University in Burnaby, Canada, during today’s conference call.


The mutation doesn’t make it impossible for men to produce viable sperm. Men with two mutated genes but otherwise healthy sperm may very well impregnate their partner without help, said Cherr. However, if these men have lower sperm counts, or less mobile sperm, the gene defect may have “a dramatic impact.”

Human sperm is of poorer quality than some primate cousins because humans tend to mate in a longer-term way than, for instance, rhesus monkeys, where multiple males pair with a female during one ovulation, said Ted Tollner, a study author and an adjunct assistant professor of obstetrics and gynecology at the University of California, Davis. That may be why the mutation hasn’t disappeared, he said.

Also, there may be some advantage to having one mutated gene and one normal one, Bevins said. Further research may include seeing if the mutation changes anything in women.

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