Mitochondrial Genetic Variation in Iranian Infertile Men with Varicocele.
BACKGROUND
Several recent studies have shown that mitochondrial DNA mutations lead to major disabilities and premature death in carriers. More than 150 mutations in human mitochondrial DNA (mtDNA) genes have been associated with a wide spectrum of disorders. Varicocele, one of the causes of infertility in men wherein abnormal inflexion and distension of veins of the pampiniform plexus is observed within spermatic cord, can increase reactive oxygen species (ROS) production in semen and cause oxidative stress and sperm dysfunction in patients. Given that mitochondria are the source of ROS production in cells, the aim of this study was to scan nine mitochondrial genes (MT-COX2, MT-tRNALys, MT-ATP8, MT-ATP6, MT-COX3, MT-tRNAGly, MT-ND3, MT-tRNAArgandMT-ND4L) for mutations in infertile patients with varicocele.


METHODS
In this cross-sectional study, polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and DNA sequencing were used to detect and identify point mutations respectively in 9 mitochondrial genes in 72 infertile men with varicocele and 159 fertile men. In brief, the samples showing altered electrophoretic patterns of DNA in the SSCP gel were sent for DNA sequencing to identify the exact nucleotide variation.


RESULTS
Ten type nucleotide variants were detected exclusively in mitochondrial DNA of infertile men. These include six novel nucleotide changes and four variants previously reported for other disorders.


CONCLUSIONS
Mutations in mitochondrial genes may affect respiratory complexes in combination with environmental risk factors. Therefore these nucleotide variants probably lead to impaired ATP synthesis and mitochondrial function ultimately interfering with sperm motility and infertility.
Department of Biology, Faculty of Science, Yazd University, Yazd, Iran.
Mohammad Mehdi
MM
Heidari
Department of Biology, Faculty of Science, Yazd University, Yazd, Iran.
Mehri
M
Khatami
Department of Biology, Ashkezar Islamic Azad University, Ashkezar, Yazd, Iran.
Amirhossein
A
Danafar
Department of Biology, Faculty of Science, Yazd University, Yazd, Iran.
Tahere
T
Dianat
Department of Biology, Faculty of Science, Islamic Azad University Shahrekord, Shahrekord, Iran.
Ghazaleh
G
Farahmand
Research and Clinical Center for Infertility and Department of Anatomy, Shahid Sadughi University of Medical Sciences, Yazd, Iran.
Ali Reza
AR
Talebi
Infertility; Mitochondrial Genes; Mutation; Varicocele
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