Document Type : Original Article
Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
Department of Andrology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.
Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada.
Background: Infertile men with multiple morphological abnormalities of the sperm flagella (MMAF) phenotype exhibit mosaic sperm flagella abnormalities such as short, bent, coiled, and irregular flagella or absent flagella. Sperm flagellum has an ultrastructurally axonemal structure that contains a large number of proteins. A-Kinase Anchoring Protein 3 (AKAP3) is expressed in spermatozoa. It may function as a regulator of motility and the acrosome reaction. This study aims to compare the genetic changes in infertile men with MMAF phenotype with the control group.
Material and Methods: The genetic variants of the AKAP3 gene were evaluated in Sixty infertile men with MMAF phenotype and forty fertile men as controls. As exon 5 of the AKAP3 gene encodes the functional domain of this protein, it’s genetic variants were studied. Therefore, PCR – sequencing was undertaken on the DNA extracted from the control and patients’ blood samples.
Results: Sixty infertile men with MMAF phenotype and forty normozoospermic men as controls were enrolled in this study. Four haplotype variants 1378T>C (rs10774251), 1391C>G (rs11063266), 1437T>C (rs11063265), and 1573G>A (rs1990312) were detected in all patients and controls. On the other hand, a missense mutation 1499T>C (rs12366671) was observed in four patients in the homozygous form and seven patients in the heterozygous form. Notably, is mutation was not identified in the controls (P=0.04). The difference between the variations’ allele frequencies in the patient and control groups was assessed by the Fisher Exact Test.
Conclusion: In the homozygous form, this mutation changes Isoleucine to Threonine. This alternation occurs inside the AKAP4 binding domain of the AKAP3 protein. The observed variants caused no significant deviation in the secondary structure of AKAP3 protein and probably its function in spermatozoa flagella. So, these variants cannot be considered as the causes of MMAF phenotype in the studied patients.