Mutant gene 'affects male fertility'

Behind the Headlines

Friday July 22 2011

The mutation affected the sperms' performance in the laboratory

“One in four men have a mutant gene 'that makes it harder for them to have children',” the Daily Mail reported. The newspaper went on to say that “scientists have found some sperm lacks a protective protein that helps it to reach the egg”.

This report is based on a study which examined the effect of a mutation in a gene called DEFB126 on male fertility. Researchers conducted lab-based experiments and found that the mutation in question affected sperm performance in the laboratory. They also found that in couples where the man carried two copies of the mutation, it took on average about two months longer to have a baby than couples where the man only carried one or no mutated copies of the gene.

It is important to note that this genetic mutation alone is unlikely to cause infertility as most of the couples in this study did have a baby over the two-year study, even if the man carried both mutations in DEFB126. This study has identified a gene that seems to be important in male fertility; however, these findings and their implications will need to be confirmed in further research.

 

Where did the story come from?

The study was carried out by researchers from the University of California at Davis, Simon Fraser University in Canada, the University of Leicester, Anhui Medical University in China, and the University of Illinois. Funding was provided by the U.S. National Institutes of Health, the U.S. National Science Foundation, the Medical Research Council and the Wellcome Trust.

The study was published in the peer-reviewed journal Science Translational Medicine.

The findings of this study were reported accurately by most media outlets.

 

What kind of research was this?

This was laboratory-based research followed up by a cohort study. Previous animal studies had shown that a protein, β-defensin, found on the surface of sperm, helps it to move through the mucus found in the female reproductive tract and keep the female’s immune system from attacking the sperm cells. It also helps sperm attach to the surface of the female’s egg, allowing fertilization to take place.

The aim of this study was to investigate whether men who carried mutated copies of the gene DEFB126 (which makes the β-defensin protein) had more difficulty siring children. The researchers examined the mobility of sperm in the laboratory, and looking at how long it took for couples to become pregnant when the male partner carried one or more mutated copies of this gene.

 

What did the research involve?

In the laboratory portion of the study, researchers first examined whether sperm from men who carried two mutated copies of the gene DEFB126 exhibited characteristics that affect male fertility, such as low sperm count and poor movement. They then looked at the ability of sperm from these men to move through a gel that is similar to the mucus found in the female reproductive tract. They compared the movement of sperm to the sperm of men who had only one or no mutated copies of the gene.

In the cohort portion of the study, the researchers examined how common it was for men to carry one or two mutated copies of DEFB126. They then followed-up the couples up over time to see whether or not this genetic mutation was associated with difficulty getting pregnant. For this part of the study, the researchers looked at newly married couples in the Anhui province of China who had no history of infertility and were trying to get pregnant between 2003 and 2005.

The researchers extracted DNA from blood samples of 638 men within this cohort, and determined which of these men carried one or more mutated copies of the gene DEFB126. An average of 26 months later, they collected information from each of the couples on whether or not they had become pregnant and gone on to have a baby. They then analysed the data to determine whether there was an association between mutations in DEFB126 and a couple conceiving and having a baby.

 

What were the basic results?

In the laboratory portion of the study, the researchers found that sperm from men carrying two mutated copies of DEFB126 showed no signs of defect or shape changes when examined under a microscope. However, the sperm had an 84% reduction in ability to move through a gel in the lab compared with sperm from men who carried only one or no mutated copies of the gene. This suggested that the sperm might have difficulties moving through the mucus found in the female reproductive tract, which is similar to the gel used in this experiment.

In the cohort part of the study, 19% of men were found to carry two mutated copies of DEFB126, 51% carried one mutated and one normal copy of DEFB126, and 29% had two normal copies. The researchers found that 71% of couples where the man carried two mutated copies of DEFB126 became pregnant over the 26 months that they were followed up. This was compared to 81% of couples where the man carried only one or no mutated copies of the gene.

On average, couples took 17.4 months to have a baby if the man carried two mutated copies of DEFB126, compared to 15.7 months for couples when the man had at least one normal copy of the gene. This equated to a 30% reduced likelihood of having a baby in any given month (Hazard Ratio 0.7, 95% confidence interval [CI] 0.5 to 1.0).

 

How did the researchers interpret the results?

Researchers concluded that men who carried two mutated copies of DEFB126 have decreased fertility compared to men who have one or both copies of the gene. However, despite the difference in time to live birth, some of the couples in which the man carried two mutated copies of DEFB126 were still able to conceive, on average, within a year, and thus did not meet the WHO definition of infertility.

They recommend that an assessment of whether a man carried mutations in DEFB126 could be used in the assessment of male infertility, in addition to the measures currently used.

 

Conclusion

This laboratory and cohort study examined the role that a specific gene, DEFB126, plays in male fertility. It examined both a physical mechanism by which mutations in this gene may affect fertility, and looked at associations between the genetic mutation and likelihood of a couple conceiving and going on to have a baby in a sample of couples in China.

While the results suggest that DEFB126 may have an impact on the time it takes couples to conceive, this genetic mutation alone is unlikely to cause infertility. Several characteristics of the study are important to note:

  • non-genetic factors which may influence ability to conceive were not controlled for in the analysis, such as frequency of intercourse.
  • most of the couples in this study were able to conceive and have a baby, despite men carrying one or more mutated copies of DEFB126. This suggests that while the gene may play a role in fertility, men who carry two mutated copies of the gene can still have children.
  • this was in part a laboratory-based study, which used a gel that is similar in several ways to the mucus found in the female reproductive tract. However, this will not fully represent the conditions in the body.
  • if a mutation prevents male or female fertility it would be expected to become less common in the population, as people carrying it would be less likely to pass it on. The mutation in DEFB126 is very common, which would not be expected if it were having a very strong effect on male fertility. Researchers will need to investigate this puzzling finding further.

While this study is an important step towards improved knowledge of the genetic factors affecting male fertility, it is not yet clear whether genetic testing for mutations in DEFB126 will be appropriate for use in assessing reasons behind subfertility.

Links to the headlines

Clue to male infertility found. BBC News, July 22 2011

Sperm defect may affect a quarter of world's men. Daily Mirror, July 22 2011

One in four men have mutant gene 'that makes it harder for them to have children'. Daily Mail, July 22 2011

Links to the science

Tollner TL, Venners SA, Hollox EL et alA Common Mutation in the Defensin DEFB126 Causes Impaired Sperm Function and Subfertility. Science Translational Medicine 2011: 92; ra65

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