Original article
Screening for partial AZFa microdeletions in the Y chromosome of infertile men: is it of clinical relevance?

https://doi.org/10.1016/j.fertnstert.2012.03.034Get rights and content

Objective

To evaluate the frequency of complete and partial AZFa Y-chromosome microdeletions among infertile Israeli men. To review the published frequencies and histologic findings of AZFa deletions.

Design

Retrospective study.

Setting

Academic medical center.

Patient(s)

A total of 1,260 infertile Israeli men. Literature review (2000–2010) of reports on men with AZFa deletions and their testicular findings.

Intervention(s)

The DNA of 1,260 infertile men was evaluated for AZF microdeletions. The DNA of 657 of them with undetected microdeletions was analyzed for partial AZFa deletion in the USP9Y and DDX3Y genes using sequence-tagged sites beyond EAA/EMQN recommendations.

Main Outcome Measure(s)

The frequency of complete and partial AZFa microdeletions. Availability of sperm cells for intracytoplasmic sperm injection in men with complete/partial microdeletions.

Result(s)

Two men had complete AZFa deletion (a frequency of 0.28% among nonobstructive azoospermic men). None had partial AZFa deletions.

Conclusion(s)

The likelihood of finding sperm cells in men with complete AZFa deletions is negligible. Complete AZFa deletion is rare and usually associated with azoospermia and absence of sperm cells in testicular tissue. The low frequency of partial AZFa deletions and the inconsistent prospects for spermatogenesis reported in the literature question the need for routine assessment of microdeletions in genes, such as USP9Y or DDX3Y.

Section snippets

Study Participants

This work was performed between 1997–2011 at the Institute for Study of Fertility in our medical center. The DNA of 1,260 infertile men was evaluated for AZF microdeletions in the three AZF regions. Six-hundred ninety-nine men were azoospermic, 319 were severe oligozoospermic (≤5 million sperm/mL in semen), and 242 were infertile with unreported semen quality. The blood samples for which semen quality was unavailable were from men who had been referred from other Israeli fertility clinics to

Results

Seventy-two of the 1,260 patients (5.7%) had an AZF microdeletion in at least one of the AZF regions (AZFa, b, and/or c). AZF microdeletions were more frequently detected among the nonobstructive azoospermic (NOA) men (8.4%) than among the severe oligozoospermic men (3.4%). Only two NOA men had complete AZFa deletion (Fig. 1), yielding a frequency of 0.16% of the total population and a higher frequency (0.28%, 2 out of 699 men) among the NOA men. As such, AZFa represented only 2.6% of the

Discussion

The present study evaluated partial and complete AZFa microdeletions in the Y chromosome for the prevalence and prospect for complete spermatogenesis among heretofore unpublished infertile Israeli men and in all cases in the literature from 2000 to 2010. AZFa microdeletions reported up to 1999 were summarized previously (24). A complete AZFa deletion turns out to be a rare phenomenon (0.28%), even among NOA men. The negligible chances of finding mature sperm cells for artificial reproduction

Acknowledgments

The authors thank Esther Eshkol for editorial assistance and Veronica Gold and Mira Malcov for their technical help with the microsatellites.

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      Putative spermatogenesis genes on the Y chromosome have been mapped to the so called ‘‘azoospermia factor’’ (AZF) region on Yq11 which is subdivided by location from proximal to distal into AZFa (Yq11.21), AZFb (Yq11.22), and AZFc (Yq11.23) (Layman, 2003; Zorrilla and Yatsenko, 2013; Dhanoa et al., 2016). Deletions in these locations are responsible for varying degrees of spermatogenic dysfunction (Hwang et al., 2010): distinct histopathology phenotypes were correlated with the site of the microdeletion, varying from complete absence of germ cells (Sertoli Cell-Only Syndrome) in patients with AZFa microdeletions, maturation arrest at meiosis in cases with AZFb microdeletions, to hypospermatogenesis in patients with AZFc microdeletions (Costa et al., 2008; Fernandes et al., 2002; Foresta et al., 2000a; Gonçalves et al., 2017; Kamp et al., 2001; Kleiman et al., 2012; Soares et al., 2012; Sun et al., 2000; Vogt et al., 1996). Deletions of the AZFc locus occur more frequently (65–70%) than AZFa or AZFb locus (Krausz et al., 2006; Tahmasbpour et al., 2014).

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      AZFa contain two main candidate genes which are involved in spermatogenesis, one is USP9Y (ubiquitin specific peptidase 9 on the Y chromosome) also known as DFFRY and other is DDX3Y (DEAD-Asp-Glu-Ala-Asp box polypeptide 3 on the Y chromosome) also known as DBY (Lahn and Page, 1997). The mode of deletion of complete AZFa is homologous intra-chromosomal recombination occur between two provirus sequences of human endogenous retrovirus, HERV15 spaced by approximately 800 kb and located at proximal Yq11 (Kamp et al., 2001; Kleiman et al., 2012; Sun et al., 2000). The deletion of AZFa is comparatively less and cause sertoli cell only syndrome (Sun et al., 2000; Krausz et al., 2006; Nailwal and Chauhan, 2017d).

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    S.E.K. has nothing to disclose. R.A. has nothing to disclose. L.Y. has nothing to disclose. R.H. has nothing to disclose. O.L. has nothing to disclose. G.P. has nothing to disclose. H.Y. has nothing to disclose. A.B. has nothing to disclose.

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