The largest study to date into unexplained infertility in men has been conducted by UK and Estonian researchers.
Scientists at the University of Tartu, Estonia, and the Wellcome Sanger Institute, Cambridgeshire, studied the genomes of over 2300 men in Estonia, half of whom had fertility issues. They uncovered a structural variant in the Y chromosome that can predispose men to have little to no sperm production, causing them to be infertile.
Co-author Dr Pille Hallast from the University of Tartu and the Wellcome Sanger Institute said: 'Our study is the largest, most sophisticated look at the genetic variation of this particular Y-chromosomal region that can increase the risk of impaired sperm production in men. By having access to such a large number of patients... we identified a common Y-chromosome subtype that is susceptible to genetic changes leading to low sperm count, but also can go unnoticed and passed down in families until a deletion in this genomic region occurs.'
Infertility is an issue that affects around 10 percent of men in the UK, yet the cause is unknown in approximately 60 percent of cases.
The research, published in the journal e-Life, showed that the presence of the novel genetic variant, discovered on the Y chromosome, increases the risk of infertility in men up to nine-fold. Genetic analysis showed that the variant included an inversion that increases the risk of deletions of portions of DNA that are critical for the development of sperm – known as spermatogenesis.
The study outlines that the inversion itself does not appear to have links to infertility but this structural change predisposes the carrier to instability in this portion of the Y chromosome, increasing the risk of deletions arising spontaneously.
The inversion alone is relatively common in men of European descent and its prevalence in the population suggests inheritance of the subtype goes largely unnoticed until genetic deletions arise that effect sperm production and the carrier experiences fertility issues later in life.
Senior co-author of the study, Dr Chris Tyler-Smith from the Sanger Institute commented on the prevalence of this subtype: 'the biggest surprise is that a Y chromosome subtype with such a deleterious effect on fertility is present in the population at all. Why hasn't it disappeared if it is so harmful? Has it perhaps only started to have this effect on fertility recently, as sperm counts have declined for environmental reasons in the last few decades and resulted in a detrimental combination of genetics and environment?'.
Given that so many cases of low sperm production are still unexplained, this study is particularly significant for future diagnostics. Screening men for this subtype, inversion and deletion would provide a chance for carriers to make informed decisions about family planning.
Professor Maris Laan, senior co-author from the University of Tartu said: 'Being able to identify the genetic reason for these men having impaired sperm production will help give them a diagnosis and access to the support that this brings… While some deletions on the Y chromosome were previously known to interfere with sperm production, understanding at this level of detail is important for the management of male fertility issues, and in this case the options of having children early in life or preserving sperm for later use could be discussed.'