AZF deletion and spermatogenesis defects in men with Y chromosome mosaicism

Introduction. Chromosome abnormalities and microdeletions in the AZF (Yq11.2) locus of the Y chromosome are common genetic causes of male infertility caused by impaired spermatogenesis, however, the effect of their combined influence has not been sufficiently investigated. Aim: a comparative analysis of semen parameters in the Y-chromosome mosaics with and without AZF deletions. Methods. 16 male patients with Y chromosome mosaicism were examined. Chromosome analysis was done using by standard cytogenetic examination. Fluorescence in situ hybridization (FISH) was performed to identify/verify mosaicism and determine the structural Y chromosome abnormalities. The Y chromosome microdeletions were detected by multiplex PCR. The semen examination was carried out with the recommendations of the WHO Guidelines (2010). Results. Cytogenetically identifiable unbalanced the Y chromosome abnormalities were found in 13 patients (81.2%) of 16 patients. AZF deletion were detected in 8 patients (50%) of 16 patients. The patients were divided into two groups: group I - patients without AZF deletions (n=8), group II - patients with AZF deletions: AZFb+c, n=7 and AZFc (b2/b4), n=1 (n=8). Prominent difference in sperm diagnosis was revealed between the groups: in group I, there was a various degree of pathozoospermia (azoospermia - 3; oligoastenoteratozoospermia - 3; asthenoteratozoospermia - 2); in group II, only severe forms of pathozoospermia (azoospermia - 7; oligozoospermia severe - 1), as well as the frequency of oligospermia - 12.5% and 37.5%, respectively. A higher concentration of spermatozoa was found in patients without AZF deletions (group I - 15.9±31.0 million/ml, group II - 0.003±0.009 million/ml; p=0.026). There was no statistically significant difference between the average age of patients in the groups, ejaculate volume, pH and viscosity of ejaculate. Conclusion. There is high frequency of structural Y chromosome abnormalities and microdeletions in the AZF (Yq11.2) locus in the Y chromosome mosaics. Unbalanced cytogenetic Y chromosome rearrangements and pathogenic AZF microdeletions are characterized by a severe degree of spermatogenesis disorder in male patients with Y chromosome mosaicism. The preservation of fertility potential in men with Y chromosome mosaicism is possible in the absence of unbalanced rearrangements and severe types of AZF deletions.

spermatogenesis, mosaicism, Y chromosome, microdeletions, AZF locus, germ cells

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