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Vol. 39 No. 1, 2000
Mitochondrial DNA Mutation and Depletion Are Associated with Decline of Fertility and Motility of Human Sperm
Yau-Huei Wei1,2,* and Shu-Huei Kao1
1Department of Biochemistry
2Center for Cellular and Molecular Biology, National Yang-Ming University, Taipei, Taiwan 112
Yau-Huei Wei and Shu-Huei Kao (2000) Sperm
motility is one of the most important determinants of male fertility.
In this review, we discuss recent findings that mutation and depletion
of mitochondrial DNA (mtDNA) are associated with poor motility and
diminished fertility in human sperm. The mtDNA mutations were
identified and characterized by polymerase chain reaction (PCR)
techniques and DNA sequencing, and the copy number of mtDNA was
determined as the ratio between the amount of mtDNA and that of nuclear
DNA in sperm. By use of these molecular techniques we first established
that the common 4977-bp deletion and 2 novel deletions of 7345 bp and
7599 bp of mtDNA occur more frequently and in higher proportions in
spermatozoa with poorer motility and lower fertility. On the other
hand, we found that the copy number of mtDNA is lower for sperm with
poorer motility. Scores of several motility parameters of sperm
assessed by a computer-assisted semen analyzer are positively
correlated with the copy number of mtDNA. Moreover, with a transmission
electron microscope we examined spermatozoa with low levels of mtDNA
from infertile patients. We found that more than 70% of spermatozoa
exhibited normal helicoidal morphology of mitochondria packed in the
midpiece. These results indicate that depletion of mtDNA in these
spermatozoa is not due to a decrease in the number of mitochondria but
is a result of the paucity of the mitochondrial genome per se. On the
basis of these recent findings, we suggest that mutation and depletion
of mtDNA in spermatozoa may play an important role in the
pathophysiology of some male infertility.
Key words: Mitochondria, DNA mutation, Sperm motility, Infertility.
*Correspondence: Tel: 886-2-28267118. Fax: 886-2-28264843. E-mail: joeman@mailsrv.ym.edu.tw
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