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Novel mutations (8899C>T AND 8907C>T) of the mitochondrial atpase 6 gene in Iraqi asthenozoospermic patients

Author: 
Oday A. Mahdy and Ismail A. Abdul-Hassan
Subject Area: 
Health Sciences
Abstract: 

Proposed causes of male infertility include sperm motility disturbances, Y chromosome microdeletions, chromosomal abnormalities, single gene mutations, and sperm mitochondrial DNA (mtDNA) rearrangements. To investigate the etiology of decreased sperm fertility and motility of sperm and to develop an appropriate therapeutic strategy, the molecular basis of these defects must be elucidated. In this study, we aimed to reveal the relationships between the genetic factors including sperm mtDNA mutations as candidate factors for male infertility. 56 Iraqi men with a history of asthenozoospermia and 10 fertile men were recruited to the study. Mitochondrial ATPase6 gene was amplified by PCR and then analyzed by direct sequencing. Two novel nucleotide substitutions were identified in the examined mitochondrial gene (ATPase 6) in both subjects as well as in progressive and non-progressive sperms, all of which are statistically significant. Two silent novel substitutions 8899 C>T and 8907C>T in ATPase6 gene that occur without change in the amino acids of protein. These heteroplasmic silent mutations( 8899C>T and 8907C>T) were observed with a high frequency in 0-5% group of sperm motility (according to WHO criteria) which were 15%(10)and 15%(10), respectively, while these frequencies were less in the rest sperm motility groups covered in this study, also, the lowest frequencies were in the normozoospermic subjects. The highest frequencies of these mutations were in the non-progressive motile sperms cells fractions that were isolated from 40% gradient in 0-5% group of sperm motilitywhich were13.5%(9)and 12%(8) for 8899C>T and 8907C>T mutations, respectively, rather than in progressive motile sperms cells that were isolated from 80% gradient fraction. The present study clearly demonstrated that mutation of mtDNA does play important roles in the diminution of fertility and decline of various motility parameters that are important determinants of male fertility as well as it approved that the mtDNA novel mutation occurrence is possible with high frequency.

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