Partial deletions in the AZFc region of the Y chromosome occur in men with impaired as well as normal spermatogenesis

Abstract

BACKGROUND: Partial deletions of the AZFc region of the Y chromosome were reported to be a significant risk factor for oligo-/azoospermia. In this study, we assessed the occurrence and frequency of partial AZFc microdeletions in patients with spermatogenic failure and in controls with normal spermatogenesis. METHODS: In a retrospective study design, gr/gr, b1/b3 and b2/b3 deletions were analysed by multiplex PCR in 170 men with normal spermatogenesis and 348 men with non-obstructive oligo-/azoospermia. RESULTS: gr/gr deletions were found in 14 men with oligozoospermia or azoospermia (4.0%) and in three normozoospermic men (1.8%) (NS). b1/b3 deletions were found both in controls (n 5 1) and in patients (n 5 1). b2/b3 deletions were significantly more frequent in the normozoospermic (five out of 170) than in the oligo-/azoospermic men (two out of 348). Three novel partial AZFc deletion patterns were found in four oligo-/azoospermic men. No correlation with semen or other clinical parameters was found. CONCLUSIONS: The frequency of gr/gr deletions is not significantly increased in men with oligo-/azoospermia, indicating that they are not sufficient per se to cause spermatogenetic impairment and infertility. b1/b3 and b2/b3 deletions are probably irrelevant for spermatogenesis. Novel deletion patterns found exclusively in infertile men suggest that other, still unexplored partial deletions might contribute to spermatogenic failure.

Analysis of Partial AZFc (gr/gr, b1/b3, and b2/b3) Deletions in Iranian Oligozoospermia Male Patients as The Candidates of Intra-Cytoplasmic Sperm Injection (ICSI)

“…However, several groups evaluated these microdeletions in infertile men in order to illustrate their close relationship with infertility. Other studies reported significant correlations of gr/gr deletions (15)(16)(17) and insignificant associations of AZFc partial deletions with infertility in men (18)(19)(20)(21)(22). However, there are several factors that affect these results, such as demographic variations, differences in patient selection values, AZF in variable deletion regions, applying different STS markers, and environmental effects, and also the classification method used to define oligospermia with different amount of sperms varied, i.e.…”

Quantitative PCR technique for the identification of microrearrangements of the AZFc region

“…More recently, the loss of specific AZFc STS was described, permitting the rapid and simple detection of AZFc partial deletion [3,5]. Several studies using this technique had previously been published [12,[25][26][27][28]. Nevertheless, duplication or deletion followed by duplication, as already described [5], cannot be detected by this technique used alone.…”

“…The effect of AZFc microrearrangements on male fertility, in particular partial deletions, is still under discussion. Indeed, partial deletions have mainly been detected in infertile men, but several papers indicated that they were also found in fertile control men [5,[10][11][12][26][27][28]. Moreover, differences have been made between the incidence of "gr-gr" deletion and "b2-b3" deletion.…”

“…Contrary to "complete" AZF deletions, the clinical relevance of partial deletion is still discussed. Indeed, several studies have shown the existence of partial AZFc deletions responsible for the loss of one cluster of the DAZ genes in fertile men [10][11][12]. In addition to deletion, duplication events and deletion followed by duplication events were identified, but their consequence in male infertility are unknown [3,5,11,[13][14][15].…”

Susceptibility of gr/gr rearrangements to azoospermia or oligozoospermia is dependent on DAZ and CDY1 gene copy deletions

“…While in some studies the frequency of AZFc subdeletions (mainly the gr/gr) is higher in infertile men as compared to fertile controls [5,11,[20][21][22]; others have failed to confirm this association [23,24]. Based on four meta-analysis studies and a large population study involving >20,000 individuals it appears that the gr/gr deletion is a risk factor for male infertility [13,20,21,25,26]; the odds ratio is estimated to be 1.4-2.4 [5,20,21,25,26].…”