Absence of mutations in the PCI gene in subfertile men

The molecular aetiology of male subfertility is still unknown in the majority of cases and it is thought that multiple genes are involved. One of the genes that might play a role in male reproductive function is the protein C inhibitor (PCI) gene. In mice the presence of PCI is an absolute requirement for reproduction. In this study we performed a mutation screen of the PCI gene in subfertile men with severe teratozoospermia or idiopathic azoospermia. Male partners of subfertile couples with idiopathic azoospermia (n = 27) or teratozoospermia (n = 34) and men with normozoospermia (n = 34) were screened for mutations in the PCI gene by direct sequencing. Nine nucleotide variants found in the patients were not present in the initial control group and were therefore screened in an additional control group of 80 men with normozoospermia by restriction fragment length polymorphism analysis. In addition, PCI antigen levels were measured in the seminal plasma of the patients in which a potential mutation was found. In total, three new variants were exclusively present in men with idiopathic azoospermia, but are not likely to have caused the patients' phenotypes. In addition, the PCI antigen levels in seminal plasma of these three patients were not decreased. The fact that we were not able to detect causal mutations in the PCI gene does not necessarily lead to the conclusion that the PCI protein is not involved in human male fertility, but the results of our study indicate that mutations in the human PCI gene are not a common cause of reduced semen parameters in men.