title: Mitochondria-related male infertility.
abstract: 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 (DeltamtDNA). Here we show that mitochondrial respiration defects caused by the accumulation of DeltamtDNA 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 mito-mice directly demonstrates that normal mitochondrial respiration is required for mammalian spermatogenesis, and its defects resulting from accumulated mutant mtDNAs cause male infertility.
authors.affiliation: Graduate School of Life and Environmental Sciences and Center for Tsukuba Advanced Research Alliance, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8572, Japan. knakada@sakura.cc.tsukuba.ac.jp
authors.forename: Kazuto
authors.initials: K
authors.lastname: Nakada
authors.forename: Akitsugu
authors.initials: A
authors.lastname: Sato
authors.forename: Kayo
authors.initials: K
authors.lastname: Yoshida
authors.forename: Takashi
authors.initials: T
authors.lastname: Morita
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Tanaka
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Inoue
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Yonekawa
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Hayashi
mesh_terms: D000818:Animals; D004272:DNA, Mitochondrial; D005260:Female; D007248:Infertility, Male / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000235:genetics*; D017384:Sequence Deletion
chemical_list: D004272:DNA, Mitochondrial