Molecular basis of male (in)fertility.

It is obvious that the molecular basis of male (in)fertility is not a linear order of genetic events but the interaction of complex genetic networks functional in three main developmental pathways: male germ-line development, male gonad development, and male somatic development. Consequently, primary genetic switch signals should exist for linking the different gene networks and/or for starting them. There is some evidence that such switch signals are concentrated on the sex chromosomes. However multiple genes encoding gene products functional for male fertility exist also on other chromosomes (autosomes). In this review I have tried to summarize our current knowledge of the location, structure and function of these genes in the human genome and, if possible, to reveal possible interactions. Additionally, the importance of the chromosome constitution (karyotype) for male fertility is discussed by describing the impairment of meiosis in sterile men with different chromosome abnormalities. As a consequence the question must be raised whether it is not advisable to increase our research activities on the analysis of genetic networks functional for male fertility in order to increase our molecular understanding of the causative agents leading to male infertility.