Role of the AZFa candidate genes in male infertility

The AZFa region on the Y-chromosome long arm has been recently assembled in a complete sequence map contained in a contig and shown to span more than 1 Mb. It contains three genes, USP9Y, DBY and UTY, but only the former two can be at present considered candidate genes for the infertile phenotype associated with deletion of this interval. These genes have X-homologues and are expressed in many tissues, even if DBY has a shorter transcript expressed in the testis only, strengthening its role in spermatogenesis. Only few patients with gene-specific deletion have been reported and a clear genotype-phenotype relation is still lacking. While deletions or even smaller mutations in USP9Y seem to be associated with a testicular phenotype of severe hypospermatogenesis, patients with deletions of DBY may present both Sertoli cell-only syndrome and severe hypospermatogenesis. On the contrary, the phenotype of patients with deletion of both USP9Y and DBY seem to be invariably azoospermia with a testicular histology of Sertoli cell-only.