Study links high levels of nitric oxide to infertility and sperm DNA damage

Dr Iraj Amiri, embryology laboratory director at the IVF Centre, Fatemieh Hospital, Hamadan, Iran, said: “In recent years nitric oxide (NO) has been recognised as a molecule that plays an important role in regulating the biology and physiology of the reproductive system, and we know that it can affect human sperm functions, such as motility, viability and metabolism. At low concentrations it can have a positive effect on cells, but a negative effect at high concentrations.

“In our study we discovered that there were significantly higher concentrations of nitric oxide in the seminal plasma of infertile patients than in healthy men. High concentrations of NO were significantly correlated with greater sperm DNA damage, and low concentrations of NO were significantly correlated with better sperm motility.”

The researchers collected semen samples from 45 infertile patients and 70 healthy sperm donors. Most of the infertile men had low sperm counts or poor sperm motility. They measured levels of NO and used a test that can detect DNA damage and repair in individual cells (single cell gel electrophoresis (comet) assay) to determine DNA damage.

“We found that the NO levels in the infertile men were, on average, twice as high as in the fertile men,” said Dr Amiri. “However, at this stage we were unable to find the cut-off point at which NO levels switched from having a positive effect to having a negative effect.

“This study indicates that infertile men have higher levels of sperm DNA damage and NO concentration in their seminal plasma compared to fertile men, and that the sperm DNA damage may be caused by the NO.”

Dr Amiri said the infertile men may have had higher concentrations of NO because of male genital tract disease and associated factors, such as inflammation and infection, which can lead to NO over-production. There were no significant differences between the fertile and infertile men as to whether they lived in the country or in built-up, traffic-congested areas, although Dr Amiri did not rule out the role played by NO in air pollution.

“Our next step is to identify the role of some environmental factors such as air pollution, jobs, disease and smoking on over-production of NO in infertile males. We also want to find a cut-off level at which NO changes from having a beneficial effect on sperm to having a negative affect.”