المستخلص: |
The genetic factors are one of the most important factors associated with male infertility. Androgens and androgen receptor play a crucial role in spermatogenesis. The androgen receptor gene has a repetitive CAG sequence that encodes a polyglutamine tract in androgen receptor which variance in normal individuals from 9 to 36 residues across different ethnic groups. The repeats length above normal were associated with Kennedy's syndrome, whereas repeats length less than normal were associated with prostate cancer. Length of androgen receptor CAG is inversely correlated with transcriptional activity of testosterone-target genes. Previous studies have been conducted to evaluate the effect of CAG repeat length on male infertility and demonstrated contradictory results. In this study, we investigated whether length of CAG repeats are associated with spermatogenic defects by establishing the mean of repeat lengths in the infertile group and it's subgroups and compare it with fertile males. The study included cohort of 270 infertile Jordanian men from the In-vitro Fertilization unit that classified into three subgroups; Azoospermic, oligozoospermic and teratozoospermic males. As well as 169 fertile males as control. Polymerase chain reaction was used to amplify the CAG repeat area and the allele size was determined by direct sequencing. As a significant association was observed between increased length of androgen receptor CAG polymorphism and male infertility (p = 0.001). In subgroups of infertility; there were a significant associations between increased length of androgen receptor CAG polymorphism and the oligozoospermia and teratozoospermia with (p < 0.001), whereas no association was found between CAG repeat length and azoospermia (p = 0.55). On the other hand, according to distributions of allele frequency the risk of oligozoospermia was 5.5 folds greater than normal when alleles frequency >20 repeats, while risk of teratozoospermia was >10.6 folds greater than normal when allele frequency >22 repeats. Our results elucidated that long stretches of CAG repeat but within normal range might lead to androgen receptor dysfunction, contributing to infertility in Jordanian men. Current results are consistent with some and deviate from other reports for different population. Thus, ethnicity and genetic backgrounds seem to explain this discrepancy.
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