Epigenetic test offers speedy diagnosis for male infertility

Scientists have discovered genetic biomarkers that could be used to distinguish between infertile and fertile men.

An international team found specific patterns of chemical modifications, known as epigenetic marks, on the sperm DNA from a study of 21 men, which were associated with infertility. They also found that epigenetic patterns related to which of the infertile men would respond positively to hormone treatment.

'Male infertility is increasing worldwide and is recognised as playing a key role in reproductive health and disease,' said Professor Michael Skinner at Washington State University in Pullman, Washington, who led the study. 'Having a diagnostic that tells you right away your male patient is infertile and here are the treatment options that will work for him would be immensely useful.'

Researchers analysed sperm samples from 12 infertile men and nine fertile men at study enrolment, before hormone therapy, and three months after hormone therapy. The participants were treated with follicle stimulating hormone (FSH). This hormone plays an important role in sperm production in males.

Researchers extracted DNA from the sperm samples and analysed them to identify changes in molecular factors that regulate gene expression. They specifically looked at differences in DNA methylation across the sperm genomes and found different patterns or ‘epigenetic signatures’ among infertile men compared with fertile men.

After comparing the sperm of infertile males that responded to FSH therapy with the sperm of non-responding infertile males, they were also able to identify epigenetic factors to distinguish between these two groups. 

The current screening strategy for male infertility involves analysing multiple sperm samples to check for sperm count, sperm motility and sperm morphology  - all of which can take several months and prolong the time to diagnosis.  

Employing a screening strategy using epigenetic biomarkers to identify infertile males could be used to speed up the process of receiving a diagnosis, said the study authors. Upon diagnosis these biomarkers also have the potential to identify males that would be responsive to treatment.

The researchers have set up a larger clinical trial to test their new diagnostic approach for male infertility. They believe harnessing epigenetic signatures for diagnosis could be helpful for other conditions as well.

'We are interested in investigating a similar diagnostic for determining how patients with arthritis and neurodegenerative diseases such as autism will respond to different treatments,' said Professor Skinner. 'In the area of therapeutics where many of the drugs on the market only work for a fraction of patients, this could ultimately save time, money and facilitate much better healthcare management.'

The findings were published in Nature: Scientific Reports.