The relationship between common mutations in CFTR, AR genes, Y chromosome microdeletions and karyotyping abnormalities with very severe oligozoospermia in Iranian men

Abstract

Background: Male infertility due to very severe oligozoospermia has been associated with some genetic risk factors.

Objective: To investigate the distribution of the mutations in the CFTR gene, the CAG-repeat expansion of the AR gene, also Y chromosome microdeletions and karyotyping abnormalities in very severe oligozoospermia patients.

Methods: In the present case-control study, 200 patients and 200 fertile males were enrolled. All patients and control group were karyotyped. Microdeletions were evaluated using multiplex PCR. Five common CFTR mutations were genotyped using the ARMS-PCR technique. The CAG-repeat expansion in the AR gene was evaluated for each individual using sequencing.

Results: Overall 4% of cases shows a numerical and structural abnormality. 7.5% of patients had a deletion in one of the AZF regions on Yq, and 3.5% had a deletion in two regions. F508del was the most common (4.5%) CFTR gene mutation; G542X, and W1282X were detected with 1.5% and 1% respectively. One patient was found to have AZFa microdeletion and F508del in heterozygote form; one patient had AZFb microdeletion with F508del. F508del was seen as compound heterozygous with G542X in one patient and with W1282X in the other patient. The difference in the mean of the CAG-repeats in the AR gene in patients and control groups was statistically significant (P = 0.04).

Conclusion: Our study shows the genetic mutations in men with severe oligozoospermia and given the possibility of transmission of these disorders to the next generation by fertilization, counseling and genetic testing are suggested for these couples before considering ICSI.

Keywords: AR gene; AZF regions; CAG repeat; CFTR gene; Male infertility; Very severe oligozoospermia.