Associations of Y-chromosome subdeletion gr/gr with the prevalence of Y-chromosome haplogroups in infertile patients

Abstract

Microdeletions in azoospermia factor (AZF) region on distal Yq are associated with male infertility and spermatogenic failure due to intra-chromosomal homologous recombination between large nearly identical repeat amplicons and are found in B10% of azoospermic and severe oligozoospermic cases. Although AZFc is deleted in azoospermia or oligozoospermia, no definitive conclusion has been drawn for the role of partial AZFc deletions to spermatogenic failure. Therefore, this study is planned to investigate the role of gr/gr subdeletions in individuals with spermatogenic failure and to find its relationship with Y chromosome haplogroups (HGs) in infertile men from Indian population. It is a case-control study involving 236 azoospermic, 182 oligospermic and 240 healthy normozoospermic men. We found 18 gr/gr, 11 b1/b3 and 2 b2/b3 subdeletions in azoospermic patients and 12 gr/gr, 5 b1/b3 and 4 b2/b3 subdeletions in oligospermic patients. However, we also found seven gr/gr deletions in normozoospermic men. Seven patients each with spermatogenic arrest and oligospermia who carry gr/gr subdeletions have deleted DAZ3/DAZ4 genes. A total of 11 patients with sertoli cell-only syndrome (SCOS) and 5 oligospermic patients with gr/gr subdeletions also have DAZ1/DAZ2 genes deleted indicating that deletions of DAZ genes contributed differently to damage to spermatogenic process. L1 HG is found in patients showing b1/b3 subdeletions, whereas HG H1a2 and H1b were found in normozoospermic individuals with gr/gr subdeletions. Our results provide evidence of association between the occurrence of subdeletions and male infertility as well as the severity of the spermatogenic failure.

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

“…Amongst these, the frequency of gr/gr but not b1/b3 and b2/b3 deletions was significantly higher in men with azoospermia or oligozoospermia as compared to fertile controls, none of the individuals had b2/b4 deletions. This data is in agreement with previous studies in Indian population wherein gr/gr but not b2/b3 was found to be significantly higher in infertile men as compared to controls [34]. The involvement of b1/b3 is yet controversial.…”

“…The involvement of b1/b3 is yet controversial. In the present study and that reported recently [35], b1/b3 deletions were not found to be associated with male infertility; however, Shahid et al [34] found a significantly higher numbers of infertile subjects with b1/b3 deletions. At present, the reason for such discrepant findings is unknown; to rule out an effect of sample numbers, we pooled the data from all the three studies and analysed the data statistically.…”

“…To strengthen the statistical analysis we pooled the data derived from this study and also reported earlier in the Indian population [34,35]. The results revealed that the gr/ gr deletions were significantly higher in azoospermic and oligozoospermic men.…”

“…It has been observed that not all men harbouring AZFc subdeletions (based on sY1291/sY1191 based screening) have loss of both DAZ and CDY1 gene copies [34,36]. Corroborating these observations further, copy number variations of DAZ and CDY1 genes were found to be associated with reduction in total motile sperm count in men harbouring AZFc subdeletions [37].…”

“…In the context of Indian population, the association of AZFc subdeletions and male infertility is unclear. In one study [34], gr/gr and b1/b3 but not b2/b3 deletions are associated with male infertility. However, in another study, only b2/b3 deletions were found to be associated with male infertility [35].…”