Human male infertility and Y chromosome deletions: role of the AZF-candidate genes DAZ, RBM and DFFRY

Microdeletions in Yq11 overlapping three distinct 'azoospermia factors' (AZ Fa-c) represent the aetiological factor of 10-15% of idiopathic azoospermia and severe oligozoospermia, with higher prevalence in more severe testicul opathies, such as Sertoli cell-only syndrome. Using a PCR-based screening, we analysed Yq microdeletions in 180 infertile patients affected by idiopat hic Sertoli cell-only syndrome and different degrees of hypospermatogenesis , compared with 50 patients with known causes of testicular alteration, 30 with obstructive azoospermia, and 100 normal fertile men. In idiopathic sev ere testiculopathies (Sertoli cell-only syndrome and severe hypospermatogen esis), a high prevalence of microdeletions (34.5% and 24.7% respectively) w as found, while milder forms were not associated with Yq alteration. No del etions were found in testiculopathies of known aetiology, obstructive azoos permia, normal fertile men and male relatives of patients with deletions. D eletions in the AZFc region involving the DAZ gene were the most frequent f inding and they were more often observed in severe hypospermatogenesis than in Sertoli cell-only syndrome, suggesting that deletions of this region ar e not sufficient to cause complete loss of the spermatogenic line. Deletion s in AZFb involving the RBM gene were less frequently detected and there wa s no correlation with testicular phenotype, with an apparent minor role for such gene in spermatogenesis. The DFFRY gene was absent in a fraction of p atients, making it a candidate AZFa gene. Our data suggest that larger dele tions involving more than one AZF-candidate gene are associated with a more severe testicular phenotype.