AZF and DAZ gene copy-specific deletion analysis in maturation arrest and Sertoli cell-only syndrome

Abstract

Deletions of the AZFc region in Yq11.2, which include the DAZ gene family, are responsible for most cases of male infertility and were associated with severe oligozoospermia and also with a variable testicular pathology. To uncover the functional contribution of DAZ to human spermatogenesis, a DAZ gene copy-specific deletion analysis was previously established and showed that DAZ1/DAZ2 deletions associate with oligozoospermia. In this study we applied the same screening method to 50 control fertile males and 91 non-obstructive azoospermic males, 39 with Sertoli cell-only syndrome (SCOS) and 52 with meiotic arrest (MA). Samples were also screened with 24 sequence-tagged sites to the different AZF regions, including 114 control fertile males. After biopsy (testicular sperm extraction, TESE), residual spermiogenesis was found in 57.7% MA and 30.8% SCOS cases (incomplete syndromes). DAZ1/DAZ2 deletions were associated with the testicular phenotype of residual spermiogenesis as they were only found in two patients (8%) with incomplete MA. Differences between incomplete (23.3%) and complete (4.5%) MA cases regarding AZFc and DAZ1/DAZ2 deletion frequencies, and between incomplete (58.3%) and complete (11.1%) SCOS cases for AZFc deletions, suggest that incomplete syndromes might represent an aggravation of the oligozoospermic phenotype. As successful TESE was achieved in 87.5% of MA cases with AZFc and DAZ1/DAZ2 deletions and in 58.3% of SCOS cases with AZFc deletions, the present results also suggest that these molecular markers might be used for the establishment of a prognosis before TESE.

Incidence of Microdeletions in the Azf Region of the Y Chromosome in Slovak Patients With Azoospermia

“…14 genes are protein-coding and 17 represent non-proteincoding transcripts [8][9][10] . Although there is still no definitive consensus about the relationship between the type of microdeletion and the resulting sperm defect, microdeletions in AZFa lead mostly to Sertoli cell-only syndrome, mutations in AZFb provoke an interruption in meiosis I, and mutations in AZFc result in hypospermatogenesis, progressing to severe azoospermia or oligospermia [11][12][13] .…”

Male infertility in Northeast China: molecular detection of Y chromosome microdeletions in azoospermic patients with Klinefelter's syndrome

“…There have been several conflicting reports about the association between KFS and AZF microdeletions (Ambasudhan et al, 2003;Ferrás et al, 2004;Foresta et al, 2005;Mitra et al, 2006;Arruda et al, 2007;Choe et al, 2007;Ceylan et al, 2010;Behulova et al, 2011). Accordingly, analysis and comparison with other studies of these associations is justified.…”

“…It was later found that microdeletions of four subregions of the AZF region (AZFa, AZFb, AZFc, and AZFd) led to various types of spermatogenesis impairments, from teratozoospermia to infertility, with different population distributions depending on their Y haplogroup profile (Li et al, 2008;Wang et al, 2010). For example, microdeletions in AZFa led mostly to Sertoli cell-only syndrome, mutations in AZFb resulted in an arrest of spermatogenesis at meiosis I, and mutations in AZFc were associated to hypospermatogenesis with progression to severe azoospermia or oligospermia (Ferrás et al, 2004;Foresta et al, 2005;Zhou et al, 2006;Arruda et al, 2007;Wang et al, 2010;Behulova et al, 2011). …”

Seminal molecular markers as a non-invasive diagnostic tool for the evaluation of spermatogenesis in non-obstructive azoospermia

“…The presence of different stages of spermatogenic cells in the testis can be confirmed by the detection of certain mRNAs, exclusively expressed at a relevant maturation level [Matzuk and Lamb 2008]. Recently, highly specific cellular and molecular methods such as flow cytometry [Koscinski et al 2005] and Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) [Bauer and Patzelt 2003;Ferras et al 2004;Patrizio et al 2000;Song et al 2000] have been used to detect germ cells in the testis. However, molecular methods are mainly based on detecting testis specific transcripts in testicular biopsies rather than seminal fluid.…”