Male Infertility is 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 infertile, if, sperm counts are <15-20 mill/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. In addition, infertile men are dying younger and as such, spermatozoa may act as a “canary in the coalmine” for the future health prediction of men2.
Although IVF has the power to overcome infertility, this does not come without risk. For either IVF or ICSI, there are major obstetric completions including unexplained still birth, foetal growth restriction, maternal pre-eclampsia, unexplained second trimnester loss and slightly higher miscarriages3. Therefore, a precise diagnosis of male-factor fertility could not only potentially save invasive procedures such as laproscopy in females, but could "predict" the future health of an infant and indeed future health problems in the man.
As such, we have used quantitative proteomics analysis to compare spermatozoa taken from healthy, fertile individuals to that of idiopathic (unexplained) men. For the first time ever, we have finally been able to explain some aspects of idiopathic infertility. The sperm specific protein, Outer Dense Fibre 1, was virtually absent from one (infertile) male ejaculate. Remarkably, this man’s pathology and sperm morphology, “mimicked” the ODF1-konocout mouse. In a second cohort of men, we found that the sperm-specific protein, Izumo1, was incorrectly phosphorylated and as such, was not present in the correct location for sperm-egg fusion to take place. WT and phospho-mimic constucts of Izumo1 have also shed light into how this essential protein is regulated.