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

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