Mutations in Exons 1， 3， 4， and 7 of Polymerase Gamma-1:Its Correlation with Asthenospermia and Its Effects on mtDNA Mutation and 4 977 bp Deletion

Abstract: The aim of this study is to investigate the correlation between mutations in exons 1， 3， 4， and 7 of polymerase gamma-1 and asthenospermia and to study the effect of POLG1 mutations on mtDNA mutation and 4 977 bp deletion. We collected 120 semen samples from patients with asthenospermia and 101 normal semen samples from the healthy donors based on WHO criteria. The mutations of POLG1 exon 1， 3， 4， and 7 in these samples have been analyzed by sequencing. MtDNA sequences and 4 977 bp deletions have been analyzed in nine asthenospermia samples with c.948 G>A mutation， nine asthenospermia samples without c.948 G>A mutation， and in nine healthy semen. samples. The POLG1 exon 4 c.948 G>A mutation was found in 9 (7.5%) of 120 asthenospermia samples， which was significantly higher than that of the control group. The accumulated mutation frequency at the mutation sites with different mutation number was significantly higher in the asthenospermia group with c.948 G>A mutations than that of the control group， but not significantly different from the asthenospermia group without c.948 G>A mutations. The mtDNA 4 977 bp deletion rate was significantly higher in the asthenospermia group with c.948 G>A mutations (7/9， 77.8%) than that of the control group (2/9， 22.2%)， or of the asthenospermia group without c.948 G>A mutations (2/9， 22.2%). The accumulated mutation rate of mtDNA at some sites was increased in the asthenospermia samples， which was not caused by POLG1 c.948 G>A mutation. The c.948 G>A mutation increases mtDNA 4 977 bp deletion， thus affecting sperm mitochondrial function and leading to decreased sperm motility.

CSTR: 32200.14.cjcb.2014.04.0014