ORIGINAL ARTICLE

Association of partial AZFc region deletions with spermatogenic impairment and male infertility

A Ferlin¹, A Tessari¹, F Ganz¹, E Marchina², S Barlati², A Garolla¹, B Engl³, C Foresta¹

¹ Centre for Male Gamete Cryopreservation, Department of Histology, Microbiology, and Medical Biotechnologies, University of Padova, Padova, Italy
² Cytogenetics and Molecular Genetics Laboratory, Division of Biology and Genetics, Department of Biomedical Sciences and Biotechnology, University of Brescia, Brescia, Italy
³ Obstetrics and Gynaecology Unit, Hospital of Brunico, Brunico, Italy

Correspondence to:
Correspondence to:
Professor Carlo Foresta
University of Padova, Department of Histology, Microbiology, and Medical Biotechnologies, Centre for Male Gamete Cryopreservation, Via Gabelli 63, 35121 Padova, Italy; carlo.foresta{at}unipd.it

Background: Complete deletions of the AZFc region in distal Yq are the most frequent molecular genetic cause of severe male infertility. They are caused by intrachromosomal homologous recombination between amplicons—large, nearly identical repeats—and are found in 5–10% of cases of azoospermia and severe oligozoospermia. Homologous recombination may also generate different partial deletions of AZFc, but their contribution to spermatogenic impairment has not been confirmed.

Methods: In this study we analysed the prevalence and characteristics of different partial AZFc deletions and their association with spermatogenic failure. We studied 337 infertile men with different spermatogenic impairment and 263 normozoospermic fertile men using AZFc specific sequence tagged site markers and DAZ specific single nucleotide variants.

Results: We identified 18 cases of partial AZFc deletions in the infertile group (5.3%) and one case in the control group (0.4%). Seventeen deletions had the "gr/gr" pattern, one the "b2/b3" pattern, and one represented a novel deletion with breakpoints in b3 and b4 amplicons. Partial AZFc deletions were associated with different spermatogenic phenotypes ranging from complete azoospermia to only moderate oligozoospermia.

Conclusions: Together with published data, our analysis of DAZ gene copy suggested that the contribution of the different deletions to male infertility varies: only partial AZFc deletions removing DAZ1/DAZ2 seem to be associated with spermatogenic impairment, whereas those removing DAZ3/DAZ4 may have no or little effect on fertility. These data show that, beside complete AZFc deletions, specific partial deletions represent a risk factor for male infertility, even if with different effect on spermatogenesis.

Abbreviations: SNV, single nucleotide variant; STS, sequence tagged site

Keywords: AZF; DAZ; male infertility; spermatogenesis; Y chromosome

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