Mitochondrial DNA may predict male fertility

A single-measure biomarker in sperm could replace traditional measures of male fertility, study shows.

A team of researchers from the University of Massachusetts Amherst, USA, observed that high sperm mitochondrial DNA copy number (mtDNAcn) can predict male reproductive health and pregnancy success among couples. This discovery may have an impact for couples seeking infertility care but could also provide a more accurate predictor of male infertility for the clinics, replacing routinely used semen parameters.

'Clinically, the diagnosis of male infertility really hasn't changed in decades,' commented Dr Richard Pilsner, corresponding author of the study published in the journal Human Reproduction. 'In the last 10 to 20 years, there have been major advances in the understanding of the molecular and cellular functions of sperm, but the clinical diagnosis hasn't changed or caught up.'

Mitochondrial DNA, which is generally inherited from the mother, decreases eight-to-tenfold during the development of mature sperm to ensure low content upon fertilisation. Previous research by Dr Pilsner and colleagues had shown that increased sperm mtDNAcn and mitochondrial DNA deletions (mtDNAdel) were associated with poor semen quality and lower odds of fertilisation in men seeking fertility treatment.

Dr Pilsner said: 'The logical next step was to determine if the associations between sperm mitochondrial biomarkers and fertilisation among couples seeking infertility treatment could be extended to couples from the general population.'

In their new publication, the researchers analysed 384 semen samples from the Longitudinal Investigation of Fertility and the Environment (LIFE) study, which looked at the relationships between lifestyle and human fertility among 501 couples from Michigan and Texas between 2005 and 2009. They found that men with higher sperm mtDNAcn had up to 50 percent lower odds of cycle-specific pregnancy and 18 percent lower probability of pregnancy within 12 months.

Future research will have to examine the impact of low mtDNAcn and factors underlying these changes in sperm mitochondrial DNA, which could include environmental toxins or other causes of inflammation and oxidative stress, the scientists hypothesised. However, they hope that the biomarker will replace semen parameters, such as sperm count, volume and motility, as a more accurate predictor of male infertility.

'Understanding what is causing the retention of mitochondrial copy number during spermatogenesis will help us come up with better platforms to intervene and to promote better reproductive success,' Dr Pilsner said. 'We need to take advantage of our understanding of the molecular toolkit that we have to develop a better predictor of male fertility, as well as fecundability.'