Genetic aspects of male infertility

Genetic factors affecting male infertility are reviewed. Male infertility is classified under four general causes: spermatogenic disorder, obstruction of the seminal tract, inflammation, sexual disorders. Idiopathic spermatogenic disorder accounts for more than 50% of all of them. The cause of spermatogenic disorder is not yet identified. In recent years it has become obvious that some of the crucial genes expressed during male germ cell differentiation exist on the long arm of Y chromosome (Yq). Identification of a gene specifically involved in sperm production could provide a more rational basis for the treatment of male infertility. In this paper I review the history of azoospermia factor (AZF), which is involved in sperm production, and describe our research on a novel AZF candidate. In 1993 Ma and coworkers isolated an AZF candidate named YRRM; and in 1995 Reijo and coworkers reported another AZF candidate known as DAZ. The existence of additional genes on Yq is strongly suspected. We are now seeking a novel AZF candidate using positional cloning and an exon trapping method. The candidate should be included in the YAC yOX21 covering microdeleted portion of Yq found by analyzing DNA obtained from many infertile men. Several unknown sequences were identified by the analysis. Ongoing studies on AZF will prove useful in the diagnosis and treatment of male infertility.