Gene Defect May Explain Infertility in Some Men

Sperm from men with at least 1 working copy of a gene called DEFB126 have a protein-sugar coating (indicated by green fluorescence, top panel) that helps them swim through cervical mucus in the female reproductive tract to reach an egg, while sperm lacking this protein-sugar coating (bottom panel) have difficulty swimming though mucus. (Image: Theodore L. Tollner, PhD)

In an article appearing today in Science Translational Medicine, a research team led by investigators from the University of California, Davis, reports that a gene variant commonly found in men results in the absence of a protein that coats human sperm, an effect that may help explain some cases of male infertility.

The protein, called DEFB126, belongs to a class of molecules called defensins, natural antimicrobial substances found on mucosal surfaces. Sperm coated with DEFB126 and sugars are better able to avoid a potential attack by a woman’s immune system—which could misidentify the sperm as a foreign body—and swim through the cervical mucus to an egg.

Worldwide, an estimated 10% to 15% of couples at some point experience infertility, defined as the inability to conceive after 1 year of unprotected intercourse. About half of these cases involve male fertility problems. But in approximately 70% of cases of male infertility, the problem cannot be explained by a low sperm count or poor sperm quality. The researchers suggested that some of this unexplainable infertility may be the result of a mutated DEFB126 gene, noting that an estimated 25% of all men carry 2 copies of the defective gene, meaning that all of their sperm have difficulty swimming through cervical mucus.

After identifying this gene defect, the researchers studied about 500 married couples in China with a history of infertility who were attempting to have their first child. They found that the birth rate was 30% lower among couples in which the husband carried 2 copies of the defective gene than for the other couples in the study.

In the future, testing men to see if they have this common mutation could help direct treatment for infertile couples, the researchers said. “Development of a diagnostic would enable couples who are trying to become pregnant to bypass extended clinical workups and move directly to the appropriate intervention,” said research team member Scott A. Veneers, PhD, MPH, of Simon Fraser University in Burnaby, British Columbia, Canada, at a press conference. For men with the defective DEFB126 gene, intracytoplasmic sperm injection, a form of in vitro fertilization in which sperm are injected directly into eggs, could be a possible option.

Categories: Genetic Counseling/Testing/Therapy, Genetics, Men's Health