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Missing Protein May Be Cause of Unexplained Infertility in Men

In some men, their sperm cells lack a protective cover and researchers say there’s a high probability they will be destroyed by the female’s immune system, which treats the sperm like a foreign invader.

An international team of scientists says it has found a possible cause of male infertility in up to one-third of all cases worldwide - a defect in a gene that normally makes it easier for the male sperm to fertilize the female egg. The discovery is likely to lead to a new test and targeted treatments for infertile couples.

In normal sperm, a protective protein called DEFB126 coats the surface of the tiny cells, allowing them to swim successfully through the female reproductive tract toward the unfertilized egg.

In men with two defective copies of the gene, their sperm cells lack this protective cover and researchers say there’s a high probability they will be destroyed by the female’s immune system, which treats the sperm like a foreign invader.

Scientists at the University of California Davis discovered DEFB126 by accident while working on a male birth control vaccine that would temporarily make men infertile.

Charles Bevins is an immunologist at UC Davis who helped discover the gene’s effect on male fertility.

“This type of fortuitous discovery is of the type that makes a scientist almost giddy with excitement. But it also raises much concern because in laboratory science, often what seems to be too good to be true, is,” Bevins said.

Bevins and scientists in Canada, China and Great Britain examined the sperm of 500 newly married men in China who were trying to conceive their first child, and then followed the couples for two years.

The investigators, led by Scott Venners of Simon Fraser University in British Columbia, Canada, found a 30 percent lower birth rate among the couples in which the husband had two copies of the gene mutation.

“So this most likely indicates that the mutated DEFB126 gene reduced the rate of conception in these couples and it took them longer to achieve a pregnancy,” Venners said.

Researchers say men who have the genetic defect might still conceive, but their sperm is 20 percent less likely to penetrate vaginal mucus and survive all the way through to conception.

Experts say approximately 70 percent of infertility cases cannot be explained by sperm quality or count. It's possible the new finding offers a long sought answer to why some couples can’t conceive even though the husband has healthy-looking sperm.

Gary Cherr is an environmental nutritionist and toxicologist at UC Davis and co-author of the study. Cherr predicts an inexpensive test will soon be developed to tell couples whether the male partner has a DEFB126 gene mutation.

“Such a development of a diagnostic like this would enable couples who are trying to become pregnant to be able to bypass extended clinical work-ups and move directly to the appropriate intervention, once it’s known whether this particular gene mutation is present,” Cherr said.

In the short term, Cherr says couples who learn they have the mutation could try to conceive a child using methods that bypass the female reproductive tract, such as artificial insemination or invitro fertilization.

Ideally, Cherr says, scientists might one day develop a vaginal cream that women could use to correct the genetic defect in male sperm so they can conceive naturally.

An article on the DEFB126 gene mutation and reduced male fertility is published in the journal Science Translational Medicine.