Loss of protein that acts as a “Klingon cloaking device” may be underlying cause of male infertility — protein allows sperm to swim through mucus.
(From left) Charles Bevins, Gary Cherr and Ted Tollner of UC Davis
The loss of a protein that coats sperm may explain a significant proportion of infertility in men worldwide, according to a study by an international team of researchers led by UC Davis. The research could open up new ways to screen and treat couples for infertility. A paper describing the work is published today (July 20) in the journal Science Translational Medicine.
The protein DEFB126 acts as a “Klingon cloaking device,” allowing sperm to swim through mucus and avoid the immune system in order to reach the egg, said Gary Cherr, a professor at the UC Davis Bodega Marine Laboratory and Center for Health and Environment. Cherr is co-senior author of the paper with Charles Bevins, professor in the Department of Medical Microbiology and Immunology.
But the UC Davis researchers found that many men carry a defective gene for DEFB126. A survey of samples from the U.S., United Kingdom and China showed that as many as a quarter of men worldwide carry two copies of the defective gene — which may significantly affect their fertility.
Infertility affects 10 to 15 percent of the U.S. population, said John Gould, associate professor of urology at UC Davis, who was not involved in the research. About half of those cases involve problems with male fertility.
One of the mysteries of human fertility is that sperm quality and quantity seem to have little do with whether or not a man is fertile, said Ted Tollner, first author of the paper, who carried out the work as a postdoctoral scholar with Cherr. Tollner is now an adjunct assistant professor in the UC Davis Department of Obstetrics and Gynecology.
“In 70 percent of men, you can’t predict their fertility on the basis of sperm count and routine assessment of sperm quality,” Cherr said. Studies like this may give us opportunities to explain these cases, Gould said.
If the discovery were successfully developed into a test, it could be used to send couples directly to treatment with intracytoplasmic sperm injection or ICSI, in which eggs are removed from the woman and injected directly with sperm, avoiding an expensive workup to exclude other causes, Gould said.
Tollner and Cherr were looking for ways to make contraceptive vaccines when they started looking at DEFB126. The protein belongs to a class of molecules called defensins, natural germ-killers found on mucosal surfaces. DEFB126 is produced in the epididymis, the structure where sperm are stored after they are produced in the testes, and deposited onto sperm in the epididymis to form a thick coat.
Tollner and Cherr were trying to make antibodies to the human protein, without much success. So they enlisted the help of Bevins, an expert on defensins who had just joined UC Davis.
Bevins’ lab made a recombinant copy of the human DEFB126 gene, with the aim of generating a purified protein that Tollner and Cherr could use to create antibodies. On their first attempt, they found the gene had a mutation that prevented it from making a protein. But when they used sperm from a different donor, they were able to make the normal protein.
Recent Comments