Male infertility: screening of azoospermia factor (azf) microdeletion in idiopathic infertile men

Abstract

Genetic factors cause about 15% of male infertility and microdeletions of Y chromosome is one of the genetic causes in idiopathic infertile men. Azoospermia factors (AZFa, AZFb, and AZFc) on Yq long arm are most important for spermatogenesis. For analysis of microdeletions in the AZF regions by sequence-tagged-site (STS) PCR is important screening method for infertility. An attempt has been made to evaluate the frequencies of microdeletions of AZFa, AZFb, AZFc in idiopathic cases of azoospermic and oligozoospermic subjects. Total 160 subjects (90 oligozoospermia and 70 azoospermia) and 50 control subjects were analyzed in this study. DNA samples were analyzed for microdeletions of Y chromosome by PCR-screening of 18 STS markers from different locus of the AZFa, AZFb, AZFc on Yq and SRY on Yp. The semen analysis was done and infertile men showing normal karyotype only were included in the study. Plasma follicle stimulating hormone (FSH) and leutinizating hormone concentrations were determined to rule out hormonal abnormality. Out of 160 analyzed cases, 17 (10.6%) subjects showed partial deletion of AZF regions, of which deletion in AZFc region was the most common (58.8%) and it was followed by AZFb and AZFa. The four subjects were shown two or more STS primer deleted sites and overall frequency of Y chromosome microdeletion in our subjects is 10.6%. The sites and sizes of deletions varied among patients. No deletions observed in control subjects. The varied frequencies of Y microdeletions are reported in infertile men in Indian population. From the results of this study it can be suggest that the frequency of deletions may be affected by study sample size, selection criteria of subjects and different geographical region. So, the screening of Y microdeletions is necessary along with the chromosomal analysis in case of infertile men.

Prevalence of Y chromosome microdeletion in azoospermia factor subregions among infertile men from West Bengal, India

“…Among all tested STS makers that we used for microdeletions screening, the STS sY254 & sY255 have been identified as most informative and these two cover the DAZ (Deleted in Azoospermia) gene. DAZ , a gene with multiple copy numbers containing several palindromic repetitive sequences in AZFc region, whose reduction of copy number enhances the risk of male infertility (Ambulkar & Pande, 2017 ). In the earlier study, it was evident that the deletions of the DAZ gene marked by sY254 and sY255 are co‐incidental (Krausz et al, 2014 ).…”

“…Another study claims 8.5% Yq microdeletions among 340 azoospermic Indian men subjected to analysis (Thangaraj et al, 2003 ). Thorough and consecutive studies from Central India in the years 2014, 2015, and 2017 reported the frequency of Yq microdeletion as 8.33%, 12.8%, and 10.6%, respectively (Ambulkar et al, 2014 ; Ambulkar et al, 2015 ; Ambulkar & Pande, 2017 ). As stated by the previous studies, AZFc appears to be the region most susceptible to deletion in azoospermic or oligozoospermic men.…”

AZF deletions in Indian populations: original study and meta-analyses

“…The global frequency of Y chromosome microdeletions is reported to range from 1 to 55.5% [22]. We found microdeletions in Indian population from a minimum of 0.59% to a maximum of 32.62% with an average of 13.48% [2,[5][6][7][8][9][10][11][12][13][14]. The phenotype associated with AZF deletions varies from azoospermia to normozoospermia depending upon the size of deletion and the genetic background of the population.…”

“…A few studies over the last two decades have analyzed Ydeletions in various populations across the world (Fig. 1) and Indian sub-continent [2,[5][6][7][8][9][10][11][12][13][14]. Most of these studies supported the association of Y-deletions with male infertility; however, the frequency of different deletions varied across the studies.…”

Association of Y chromosome AZF region microdeletions with recurrent miscarriage in Iranian couples: A case–control study

“…Recent studies have discussed the role of abnormalities in men's sperm genomes, such as chromosomal abnormalities, chromatin fragmentation, and microdeletions in the azoospermia factor (AZF) region, on frequent miscarriages in their wives (Pal et al., 2018 ; Tan et al., 2019 ). Infertility has been linked to microdeletions of the Y chromosome in numerous studies (Ambulkar & Pande, 2017 ; Kaminski et al., 2020 ; Liu et al., 2016 ; Pylyp et al., 2015 ), so it is also possible that repeated abortions are related to these microdeletions. The prevalence of AZF region microdeletions in men can vary from 2% to 10%, depending on the society (Zargar et al., 2020 ).…”