Analysis of candidate male infertility genes

Project Details


Male infertility, which accounts for ~30% of the fertility problems, is usually associated with a decreased production of spermatozoa. Causes can be acquired or inherited, though in ~70% of the cases the cause of the abnormal sperm production remains unknown. Most probably, genetic causes will explain part of the fertility problems. In recent years, intensive research has been performed by our group and other researchers to identify genetic male infertility factors.
In previous studies in our research center, deletions on the long arm of the Y chromosome have been investigated. The relationship between male infertility and Yq microdeletions is obvious. One of the genes located on the long arm of the Y chromosome and studied in our laboratory, is the PRY gene. This gene is presumably not involved in spermatogenesis, but a function in apoptosis might be possible. A relationship between high number of apoptotic sperm cells and abnormal sperm parameters has been suggested in multiple studies. In this case, the PRY gene might have an indirect role in male infertility. More recent research is focused on the identification of genes on the X chromosome that are only expressed in testicular tissues. Recently, three changes have been observed in the X-linked USP26 gene of eight patients with Sertoli cell-only syndrome. These changes could not be detected in men with proven fertility.
The aim of the first study is to gain more insight into apoptosis of human spermatozoa. In men with abnormal semen parameters, a higher frequency of sperm cells with apoptotic characteristics have been detected. On the one sight apoptosis can be considered as a protection against the inheritance of defects at the DNA level, but on the other sight abnormal regulation of apoptosis might cause the elimination of 'healthy' sperm cells. However, it remains unknown whether spermatozoa have the capacity to induce apoptosis themselves. Therefore, we will investigate whether it is possible to induce apoptosis in ejaculated and purified spermatozoa.
A second study is focused on the identification of genes that are potentially involved in spermatogenesis and might be important in the etiology of male infertility. Special attention is paid to genes located on the X chromosome since men only have a single copy of these genes. Mutations in genes located on the sex chromosomes will have an immediate impact since compensation by a second, normal copy is not possible. The expression of genes of interest (NXF2, USP26) will be analyzed at the RNA and protein level. The role of these genes in the etiology of male infertility will be investigated by exploring mutations in the DNA of infertile men.
Effective start/end date1/01/0731/12/08

Flemish discipline codes

  • Basic sciences


  • fertility