Mutations In The Exon A Of Androgen Receptor Gene In Males With Idiopathic Azoospermia And Severe Oligozoospermia

Objective: Infertility affects about 10% of all couples trying to conceive, and male infertility is about 30%. There are many causes of male infertility, such as mumps. The causes in most cases are still uncertain, we call them idiopathic infertility. Androgen , mainly testosterone and 5α-dihydrotestosterone, are essential regulators of human spermatogenenesis. Their action is mediated by the androgen receptor, so the disruption of the androgen receptor gene will results in androgen insensitivity syndrome (AIS). Patients with complete AIS have normal male levels of testosterone but are completely female in external appearance, but the minimal androgen insensitivity only result in defective spermatogenesis and male infertility. So androgen receptor gene is very important to male infertility. Androgen receptor gene has 8 exons, because the exon A is very long,we divided it into 5 fragments. The mutations of the exon A will decrease the transactivation function and the regulation function of the target genes. Preparation of genomic DNA and determination of the mutations are got by molecule biological method. We analyzed the association between themutations and the idiopathic azoospermia and severe oligozoospermia.Methods: 36 male infertility patients were entrered into our study, including 20 men of severe oligozoospermia and 16 men of idiopathic azoospermia. We selected 40 fertile control men too. DNA was extracted from blood leukocytes, and the polymerase chain reaction was used to amplify the second and the third fragments of exon A. The primer were designed as previously published: A2: 5,- C A C A G G C T A C C T G G T G C T G G A-3,,5,- C T G C C T T A C A C A A C T C C T T G G C-3,；A3:5,- G C T C C C A C T T C C T C C A A G G A C A A -3,,5,-C G G G T T C T C C A G C T T G A T G C G-3,). The length of A2 is 416 bp, and the length of A3 is 528 bp. The amplified products were separated by agarose, the insertion and deletion mutations can be detected. Single strand conformational polymorphism analysis was carried out on these products to screen for point mutations. Results: We did not detect abnormalities in any of the control's DNA samples (0%). 5 of 36 patients had androgen receptor gene mutations (13.8%). All the mutations are point mutations. No gross deletions or insertions were detected. The mutation rate of infertile men is 13.8%, yet the rate of the normal control is 0%, there are significant difference between the two groups ( X2=3.90;p<0.05).Conclusion: The mutation of A2 and A3 within the exonA of the androgen receptor gene is one of the important reasons of the idiopathic infertility. And we should detect the mutations of the androgen receptor gene of the infertility patients with unknown causes, it is very helpful to clear-out the reasons.