Sperm face steep odds when set free to fertilize an egg. A slightly faulty tail, a miscalibrated electrical charge on their cell membrane or some other subtle defect can keep these genetic couriers from becoming the lucky, lone swimmer that sires offspring.
And now it seems that a surprisingly common genetic mutation might decrease a man's chances of having viable sperm even further. According to a study published online July 20 in Science Translational Medicine, roughly a fifth of the male population may suffer lower fertility because of this mutation, and half of all men may be carriers of the trait.
The frequency of the variation is surprising because natural selection quickly removes most genetic traits that limit sexual success from the gene pool.
Not so with this mutation, according to Gary Cherr of the department of environmental toxicology and nutrition at the University of California, Davis and his co-authors on the study. They estimate that this allele, or form of the gene, is present in some 50 percent of men. In the team's investigations, having just one of the mutant alleles did not seem to decrease a man's likelihood of fathering a child. But about 20 percent of men in the study samples had two copies of the gene mutation, which, especially when combined with other factors—such as low sperm count or decreased sperm swimming ability—diminished chances for conception.
The gene in question, DEFB126, helps to manufacture a protein that coats sperm in a sugary carbohydrate. Without that protective coating, sperm seemingly have trouble evading the immune defenses inside the female reproductive tract and "are typically rapidly dispatched," said Cherr at a press briefing on the paper Wednesday.
The recent research followed hundreds of couples in China who were trying to have their first child and had no known fertility issues. Couples in which the man had two copies of the genetic mutation were about 30 percent less likely to become pregnant or have a child within two years. Although the infertility link will need to be tested in other populations, the researchers said that they had also found similar frequencies of the genetic mutation in European and African samples.
Why would such a seemingly disadvantageous genetic mutation remain so common in the population? The researchers are scratching their heads over that question, too, but they suggested at the press conference that there might be some as-yet undiscovered advantage to having the mixed genetic makeup of one mutated gene and one normal one. If so, natural selection might favor retaining the mutation at a fairly high frequency despite its disadvantages.
About 13 to 14 percent of all couples in their reproductive years experience infertility, which is defined as being unable to conceive after one year of trying. The roots of infertility are split fairly evenly between the sexes, but about 17 percent of cases have no apparent biological basis. Men with the newly discovered genetic mutation often have sperm that appear perfectly normal to standard evaluations. Thus this genetic variation "potentially clouds interpretation of male fertility," said another of the paper’s co-authors, Theodore Tollner of the department of obstetrics and gynecology at U.C. Davis,at the Wednesday briefing.
As Steve Rozen of the Duke Graduate Medical School in Singapore notes in an essay in the same journal about the new paper, it is "too soon to predict" how knowledge of the mutation will affect efforts to overcome infertility. But Tollner and his colleagues suggested that screening for the mutation (possibly even with an at-home genetic test in the near future) could become a first step for suspected low fertility or infertility. And if all the sperm need is the protein coating, an answer to the problem could be as simple as a vaginal gel that could deliver the missing layer to sperm (a method that has already been shown to work in monkeys but has yet to be tested in—or approved for—humans).
So if the new link is supported by future research, it might help doctors and couples get to the bottom of their conception conundrum sooner—and recommend the appropriate remedy, whether that might be artificial insertion of sperm or in vitro fertilization (IVF). This clarity could reduce "costly protracted clinical evaluations and emotional stress" that often accompanies difficulties conceiving, the team wrote in their paper. "Knowing right up front if this mutation is present can give you a lot of important information and lead you down the right path," Tollner said.