Mitochondria-Related Male Infertility

Approximately 15% of human couples are affected by infertility, and about half of these cases of infertility can be attributed to men, through low sperm motility (asthenozoospermia) or/and numbers (oligospermia). Because mitochondrial genome (mtDNA) mutations are identified in patients with fertilit...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2006-10, Vol.103 (41), p.15148-15153
Main Authors: Nakada, Kazuto, Sato, Akitsugu, Yoshida, Kayo, Morita, Takashi, Tanaka, Hiromitsu, Inoue, Shin-Ichi, Yonekawa, Hiromichi, Hayashi, Jun-Ichi
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Biological Sciences
DNA, Mitochondrial
Female
Infertility
Infertility, Male - genetics
Male
Male infertility
Males
Mammals
Mating behavior
Mice
Mice, Inbred C57BL
Mitochondria - genetics
Mitochondrial DNA
Mutation
Prophase
Respiration
Rodents
Sequence Deletion
Spermatocytes
Spermatozoa
Testes
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Summary:Approximately 15% of human couples are affected by infertility, and about half of these cases of infertility can be attributed to men, through low sperm motility (asthenozoospermia) or/and numbers (oligospermia). Because mitochondrial genome (mtDNA) mutations are identified in patients with fertility problems, there is a possibility that mitochondrial respiration defects contribute to male infertility. To address this possibility, we used a transmitochondrial mouse model (mito-mice) carrying wild-type mtDNA and mutant mtDNA with a pathogenic 4,696-bp deletion (ΔmtDNA). Here we show that mitochondrial respiration defects caused by the accumulation of ΔmtDNA induced oligospermia and asthenozoospermia in the mito-mice. Most sperm from the infertile mito-mice had abnormalities in the middle piece and nucleus. Testes of the infertile mito-mice showed meiotic arrest at the zygotene stage as well as enhanced apoptosis. Thus, our in vivo study using mitomice directly demonstrates that normal mitochondrial respiration is required for mammalian spermatogenesis, and its defects resulting from accumulated mutant mtDNAs cause male infertility.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0604641103