Massive deletion in AZFb/b+c and azoospermia with Sertoli cell only and/or maturation arrest

Summary Recent studies have revealed that AZF deletion in Y chromosome is the most common known molecular genetic cause of spermatogenetic failure leading to male infertility. Characteristics of AZFa, AZFb and AZFc deletions and their association with spermatogenic impairment have been reported in a large number of populations. However, the distributions of those larger deletions resulted from P5/proximal-P1, P5/distal-P1 and P4/distal-P1 recombinations are still unclear as the literature on their frequencies is limited, and the contribution of these deletions to spermatogenetic failure remain to be confirmed by population studies. In this study, we investigated such massive deletions in 387 idiopathic azoospermic, 269 oligozoospermic patients and 315 men with normal spermatogenesis using 21 AZFb/c specific sequence-tagged sites. As a result, nine uninterrupted massive deletions were observed exclusively in men with azoospermia caused by either Sertoli cell only (SCO) or maturation arrest (MA). Prevalence of the deletion was 2.33%, in which five deletions arose from non-allelic homologous recombination between the palindromes P5 and P1 and two between P4 and P1. In other two deletions, novel proximal breakpoints in the interval region between P4 and P3 were observed. Our findings strongly support that the massive deletions in the AZFb or AZFb+c regions are important genetic causes of SCO and/or MA resulting in azoospermia and, besides the P5/proximal-P1, P5/distal-P1 and P4/distal-P1 deletions there may be other massive deletions in these regions resulting in severe spermatogenic impairment.