Male infertility is a very common condition, with reports suggesting that one in 15 men of reproductive age is affected¹. The diagnosis of male-factor infertility is difficult and involves discounting female infertility through hormone measurements, pelvic examination and invasive laparoscopy. A semen profile analysis can suggest male infertility, if sperm counts are <15-20 million/ml, or <50% of sperm possess forward progressive motility (and < 25% rapidly progressive sperm) or <4% good morphology sperm. However, for many couples (20-30%), infertility remains largely unexplained.

Large scale cohort reports have shown that infertile men on average are dying younger than their fertile counterparts. In addition, infertile men on the whole demonstrate three times the average rates of cancer compared to the general population² . As such, it appears that spermatozoa may give a “prophetic” insight into the overall health of men with a current leading hypothesis suggesting that sperm cells may act as a “canary in the coalmine” for the future prediction of men’s health².

As such, we have used quantitative proteomics analysis to compare spermatozoa taken from healthy, fertile individuals and compared the proteome to that of an infertile male. Several proteins were found to be altered, including, the sperm specific protein, Outer Dense Fibre 1, which was virtually absent from the gametes of the infertile male. Of particular note however, the epigenetic regulation of histones was shown to be very different in the infertile sample, compared to the fertile sample. This suggests that erroneous post-translational modifications on Histones within infertile men may represent the first insight into not only male infertility, but also may explain the link between infertile gametes and the future prediction of men’s health.