Male infertility and the involvement of the X chromosome

Male infertility is a worldwide problem, keeping many researchers puzzled. Besides environmental factors, much attention is paid to single gene defects. In this view, the sex chromosomes are particularly interesting since men only have a single copy of these chromosomes. The involvement of the Y chromosome in male infertility is obvious since the detection of Yq microdeletions. The role of the X chromosome, however, remains less understood.

Articles were obtained by searching PubMed until December 2008. A first search attempted to identify genes located on the X chromosome potentially important for spermatogenesis. A second part of the study was focused on those genes for which the role has already been studied in infertile patients.

Multiple genes located on the X chromosome are expressed in testicular tissues. The function of many genes, especially the cancer-testis genes, has not been studied so far. There were striking differences between mouse and human genes. In the second part of the study, the results of mutation analyses of seven genes (AR, SOX3, USP26, NXF2, TAF7L, FATE and AKAP4) are described. Except for AR, no infertility causing mutations have, thus far, been described. It cannot be excluded that some of the observed changes should be considered as risk factors for impaired spermatogenesis.

It can be concluded that, so far, the mutation analysis of X-linked genes in humans, presumed to be crucial for spermatogenesis or sperm quality, has been disappointing. Other approaches to learn more about male infertility are necessary.