Protein coat key to male fertility

The loss of a protein that coats sperm and enables it to swim through cervical mucus may explain a significant proportion of infertility in men worldwide say an international team of researchers.

The team – led by UC Davis and involving researchers at the University of Leicester – found 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.

“One of the mysteries of human fertility of that sperm quality and quantity seem to have little to do with whether or not a man is fertile,” said Ted Tollner, first author of the paper published in Science Translational Medicine.

“In 70% of men, you can’t explain their infertility on the basis of sperm count and quality,” added Gary Cherr, senior author.

DEFB126 is a protein that belongs to a class of molecules called defensins – natural germ-killers found on mucosal surfaces. It is produced in the epididymis and deposited onto sperm to form a thick coat.

However, a survey of samples from the US, UK and China showed as many as a quarter of men worldwide carry two copies of the defective gene, while half of all men carry one defective copy. Researchers found a statistically significant decrease in the number of pregnancies in couples where the man carried two copies of the defective DEFB126 gene.

“This gene makes a significant contribution to male fertility,” said Dr Ed Hollax, lecturer in genetics at Leicester. “As many of 20% of Leicester’s men will have the variant gene that leads to reduced fertility. For these men, it may require an average of two extra months to get their partner pregnant.”

It is hoped that the finding will help treat men with infertility. Cherr said that they hope to work with a major infertility program in the US to further explore the role of the mutations.

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