Sperm 'cloak' mutation may explain infertility

Some men may be less fertile than normal because they have a genetic mutation for a protein that coats the surface of sperm, scientists have found.

Some men may be less fertile than normal because they have a genetic mutation of a protein that coats the surface of sperm, scientists have found.

Normal human sperm with green dots showing the presence of a sugary molecule that allows the sperm to swim through cervical mucus. (Courtesy of Ted Tollner)

In Wednesday's issue of the journal Science Translational Medicine, an international team of researchers said lack of the protein, called beta-Defensin 126, lowered fertility among 509 newly-married Chinese couples.

Fertility was also lower in men with the mutation who did not show other problems normally associated with infertility, such as low sperm count or reduced sperm motility.

"In 70 per cent of infertile men, you can't explain their infertility on the basis of sperm count and quality," said Gary Cherr, a professor at the University of California - Davis Center for Health and Environment and the senior author of the paper.

The findings may help to explain those cases of male infertility, and could improve current testing, which fails to find the cause of infertility in about one-fifth of infertile couples, the researchers said.

The researchers suspect that the mutation prevents the protein from being made.

The protein is a defensin, a member of a diverse family of antimicrobial proteins. In males macaques, the protein acts like a "Klingon cloaking device" that helps sperm to swim through the cervical mucus and avoid the immune system to reach the egg, Cherr said. For macaques with the protein mutation, it is harder for their sperm to get through the mucus., 

Among the newlywed Chinese couples, they were less likely to conceive within two years if the men had two copies of the mutation. The World Health Organization said a couple is considered infertile if after two years of regular sexual intercourse, without contraception, the woman has not become pregnant and there is no other reason such as breastfeeding.

Wives of men with two copies of the mutation were 30 per cent less likely to have a birth than other couples, said study co-author Scott Venners of Simon Fraser University in Burnaby, B.C.

Assisted reproduction

If a test is developed that is safe and effective, it could potentially be used by couples to guide choices about the timing and type of assisted reproduction, the researchers said.

If a man has two copies of the mutation then "resorting immediately to assisted reproduction may be attractive," Steve Rosen of Duke-NUS Graduate Medical School Singapore said in a journal commentary accompanying the study.

"This would be especially true if the woman has dwindling ovarian reserves and is also contributing to the couple's infertility. This situation is becoming more common as delayed childbearing, which results in decreased female fertility becomes more common."

It is too soon to predict how the new information may affect decisions on using assisted human reproduction, such as depositing washed sperm directly into the uterus and bypassing the cervical mucus.

The study also looked at the frequency of the gene in DNA samples in people from the U.S., United Kingdom, China, Japan and Africa.

They found that worldwide, about half of all men carry one defective copy and a quarter have two defective copies and, therefore, make sperm that are poor at swimming through mucus.

The question remains why a mutation that affects fertility seems so common. The researchers speculated it may be that men with one normal copy and one defective copy, but who have normal fertility, have some other advantage, such as resistance to infection.