We analysed the location of proteins encoded by the DAZ (Deleted in AZoospermia) genes in human testis tissue and in mature spermatozoa. The DAZ genes are known to be expressed exclusively in the human male germ line, and are candidate genes for the expression of the azoospermia factor AZFc mapped recently to distal Yq11. They encode testis-specific RNA binding proteins, the function of which is not yet known. Immunostaining experiments with antibodies prepared for the specific peptide domain encoded by the DAZ2 transcript (formerly SPGY1) revealed the presence of DAZ proteins in the innermost layer of the male germ cell epithelium and in the tails of spermatozoa. This suggests a function for DAZ proteins in the RNA metabolism of late spermatids, presumably in the storage or transport of testis-specific mRNA, the translation of which is repressed until the formation of mature spermatozoa. Deletion of DAZ genes is supposed not to interfere with human sperm maturation but to result in a gradual reduction of mature spermatozoa.

We have isolated a series of human testis poly(A) cDNA clones by cross-hybridization to SPGY1, a Y gene homologous to DAZ. Their sequence analysis revealed an identical nucleotide composition in different 'full-length' clones, suggesting that all were encoded by the same gene. We mapped this gene to the short arm of chromosome 3 and designated it SPGYLA (SPGY like autosomal). Comparison of the SPGYLA cDNA sequence with the cDNA sequences of DAZ and SPGY1 revealed two prominent differences. The tandem repetitive structure of 72 bp sequence units (DAZ repeats) is absent. SPGYLA contains only one 72 bp sequence unit. Downstream of it, a specific 130 bp sequence domain is present which is absent in DAZ and SPGY1 but present in the mouse gene Dazla and in the Drosophila gene boule. SPGYLA encodes an RNA binding protein expressed only in the human male gonad. The data presented give strong evidence that not DAZ but SPGYLA is the functional human homologue of Dazla and boule.

Different Y mutations in Yq11 occurring de novo in sterile males were first described 19 years ago. Since the phenotype of the patients was always associated with azoospermia or severe oligospermia, it was postulated that these mutations interrupt a Y spermatogenesis locus in the euchromatic Y region (Yq11) called azoospermia factor (AZF). Recently, it became possible to map AZF mutations to different subregions in Yq11 by molecular deletion mapping. This indicated that azoospermia is possibly caused by more than one Y gene in Yq11 and the Yq11 chromatin structure. The frequency of AZF mutations in idiopathic sterile males (5-20%) may indicate a need for a general screening programme for its analysis in infertility clinics.