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<em>Science Translational Medicine</em>: Defect in Sperm Protein Linked to Male Infertility

Researchers have pinpointed a genetic mutation that may help explain why some men are less fertile than normal, a new study in the 20 July issue of the journal Science Translational Medicine reports.

The gene encodes a protein called beta-defensin 126, which coats the surface of sperm and helps them penetrate cervical mucus in women. Men with a variant of this gene, called DEFB126, lack beta-defensin 126, making it much more difficult for sperm to swim through the mucus and join with an egg.

“The World Health Organization defines infertility as the inability to conceive after 12 months of attempts in the absence of birth control. Our data suggest the likelihood or probability that couples are unable to conceive in the 12-month window will increase significantly if men lack the normal gene for DEFB126,” said Gary Cherr, senior author of the study and professor at the University of California, Davis, during a 20 July teleconference with reporters

The genetic variation in DEFB126 may account for many unexplained cases of infertility. Moreover, screening for variants of DEFB126 in men could improve current testing, which still fails to find the cause of infertility in almost one-fifth of infertile couples.

Compared to sperm from monkeys and other mammals, human sperm are typically poor quality, slow-swimming, and contain a high rate of defective cells. “It’s possible that because humans, unlike most mammals, breed in long-term monogamous relationships, sperm quality just does not matter very much,” Cherr said in a news release from the University of California, Davis.

However, some researchers believe that, for reasons unknown, human male fertility has been falling worldwide in recent decades. The decline has prompted research on DEFB126, and continues to reveal fertility problems associated with the defective gene.

Study author Theodore Tollner describes how the beta defensin DEFB126 protein is applied to the sperm surface, and discusses its role in sperm transport in the female reproductive tract.
[Video created by Theodore L. Tollner, 2011; © Science/AAAS]

Examining 500 newly married Chinese couples, Cherr and colleagues found that the lack of beta-defensin 126 in men with the mutation lowered fertility, even among men that did not display other deficiencies usually associated with infertility such as low sperm count and reduced sperm motility.

Wives of men with the beta-defensin 126 variant were significantly less likely to become pregnant than women in other couples, and 30% less likely to give birth.

In a related Perspective article, Steve Rozen, a human genetics researcher at Duke-NUS Graduate Medical School in Singapore, discusses the clinical implications of the findings, particularly the possibility of treating sperm from men carrying the DEFB126 variant.

“It is clear that this genetic information could lead to more informed assisted reproduction in addition to possible new methods of treating sperm,” Rozen said.


Read the report, “A Common Mutation in the Defensin DEFB126 Causes Impaired Sperm Function and Subfertility,” by Theodore Tollner and colleagues.

Visit Science Translational Medicine.