Association of Spermatogenic Failure with the b2/b3 Partial AZFc Deletion

Abstract

Infertility affects around 1 in 10 men and in most cases the cause is unknown. The Y chromosome plays an important role in spermatogenesis and specific deletions of this chromosome, the AZF deletions, are associated with spermatogenic failure. Recently partial AZF deletions have been described but their association with spermatogenic failure is unclear. Here we screened a total of 339 men with idiopathic spermatogenic failure, and 256 normozoospermic ancestry-matched men for chromosome microdeletions including AZFa, AZFb, AZFc, and the AZFc partial deletions (gr/gr, b1/b3 and b2/b3).AZFa and AZFc deletions were identified in men with severe spermatogenic failure at similar frequencies to those reported elsewhere. Gr/gr deletions were identified in case and control populations at 5.83% and 6.25% respectively suggesting that these deletions are not associated with spermatogenic failure. However, b2/b3 deletions were detected only in men with spermatogenic failure and not in the normospermic individuals. Combined with our previous data this shows an association of the b2/b3 deletion (p = 0.0318) with spermatogenic failure in some populations. We recommend screening for this deletion in men with unexplained spermatogenic failure.

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“…In the non-Spanish cohort, consistent with the high proportion of North African patients (53.2%) included, AZF deletions were mostly found on hgr E, which is seemingly more prone to Y microdeletions. 28,29 Moreover, the deletion frequency reported in idiopathic AZ and SOZ men (9.09 and 5.5%) in Moroccan population 28 is consistent with our findings in non-Spanish idiopathic AZ and SOZ men (10.7% and 6.9%, respectively). The prevalence of Y microdeletions in our study population (3.3%) is in line with the overall data presented in the literature (3.5%, according to a recent meta-analysis 30 ).…”

“…The remaining three b2/b3 deletion carriers belonged to hrgs C,F,G,H,I, which is a frequent Y hgr in Moroccan population for which b2/b3 deletion has been recently reported in association with male infertility. 28,29 The significant association observed indicates a Y background-dependent deleterious effect of b2/b3 on spermatogenesis.…”

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“…It varies from 2.1 to 12.5 % among all cases, and from 0 to 10.2 % among normozoospermic controls [69]. In a conflicting report by Eloualid et al, [65] they have reported that gr/gr deletions occur at similar frequencies of 5.83 and 6.25 % in patient and control populations respectively, suggesting that these deletions are not associated with spermatogenic failure.…”

“…However, the prevalence of the b1/b3 deletion in the human population is very low and its frequency varies, with only 18 deletions published to date [65]. Its effect on spermatogenesis is unknown [66].…”

“…Its effect on spermatogenesis is unknown [66]. The b2/ b3 deletion removes 1.8 Mb of AZFc or DAZ3/DAZ4 genes and was detected only in men with spermatogenic failure [65]. The gr/gr deletion [67,68] removes half of the AZFc region including two copies of the DAZ gene family (DAZ1/DAZ2), one copy of the CDY1 gene family (CDY1a) and one copy of the BPY2 gene [66].…”