title: Quantitative and qualitative changes of mitochondria in human preimplantation embryos.
abstract: OBJECTIVE
  The oxygen consumption rates (OCRs) in mice and cattle have been reported to change during preimplantation embryogenesis. On the other hand, mitochondrial DNA (mtDNA) copy number has been shown to be unchanged in mice and changed in cattle and pigs. The interactions between mitochondrial functions and mtDNA copy numbers in human embryos during preimplantation development remain obscure.
  
  
  METHODS
  Sixteen oocytes and 100 embryos were used to assess mtDNA copy numbers and OCR. Three oocytes and 12 embryos were used to determine cytochrome c oxidase activity. All specimens were obtained between July 2004 and November 2014, and donated from couples after they had given informed consent. Mature oocytes and embryos at 2-14-cell, morula, and blastocyst stages were used to assess their OCR in the presence or absence of mitotoxins. The mtDNA copy number was determined using the samples after analysis of OCR. The relationships between developmental stages and OCR, and developmental stages and mtDNA copy number were analyzed. Furthermore, cytochrome c oxidase activity was determined in oocytes and 4-cell to blastocyst stage embryos.
  
  
  RESULTS
  The structure of inner mitochondrial membranes and their respiratory function developed with embryonic growth and the mtDNA copy numbers decreased transiently compared with those of oocytes. The undifferentiated state of inner cell mass cells appears to be associated with a low OCR. On the other hand, the mtDNA copy numbers increased and aerobic metabolism of mitochondria increased in trophectoderm cells.
  
  
  CONCLUSIONS
  The mitochondrial respiratory function of human embryos developed along with embryonic growth although the copy numbers of mtDNA decreased transiently before blastulation. OCRs increased toward the morula stage ahead of an increase of mtDNA at the time of blastulation. Data regarding changes in mitochondrial function and mtDNA copy number during preimplantation development of human embryos will be useful for the development of ideal culture media.
authors.affiliation: IVF Namba Clinic, 1-17-28 Minamihorie, Nishi-ku, Osaka, 550-0015, Japan. hashimoto@ivfnamba.com.
authors.forename: Shu
authors.identifier: http://orcid.org/0000-0001-9083-1403
authors.initials: S
authors.lastname: Hashimoto
authors.affiliation: Department of Obstetrics and Gynecology, Hyogo College of Medicine, Nishinomiya, Hyogo, 663-8501, Japan.
authors.forename: Naoharu
authors.initials: N
authors.lastname: Morimoto
authors.affiliation: IVF Namba Clinic, 1-17-28 Minamihorie, Nishi-ku, Osaka, 550-0015, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Yamanaka
authors.affiliation: IVF Namba Clinic, 1-17-28 Minamihorie, Nishi-ku, Osaka, 550-0015, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsumoto
authors.affiliation: IVF Namba Clinic, 1-17-28 Minamihorie, Nishi-ku, Osaka, 550-0015, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yamochi
authors.affiliation: IVF Namba Clinic, 1-17-28 Minamihorie, Nishi-ku, Osaka, 550-0015, Japan.
authors.forename: Hiroya
authors.initials: H
authors.lastname: Goto
authors.affiliation: IVF Namba Clinic, 1-17-28 Minamihorie, Nishi-ku, Osaka, 550-0015, Japan.
authors.forename: Masayasu
authors.initials: M
authors.lastname: Inoue
authors.affiliation: IVF Namba Clinic, 1-17-28 Minamihorie, Nishi-ku, Osaka, 550-0015, Japan.
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Nakaoka
authors.affiliation: Department of Obstetrics and Gynecology, Hyogo College of Medicine, Nishinomiya, Hyogo, 663-8501, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shibahara
authors.affiliation: HORAC Grandfront Osaka Clinic, Osaka, 530-0011, Japan.
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Morimoto
mesh_terms: D001755:Blastocyst; D056915:DNA Copy Number Variations / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics*; D047108:Embryonic Development / Q000235:genetics*; D005260:Female; D006801:Humans; D008928:Mitochondria / Q000235:genetics; D009028:Morula / Q000378:metabolism; D009865:Oocytes / Q000254:growth & development; D009866:Oogenesis / Q000235:genetics*; D011247:Pregnancy
chemical_list: D004272:DNA, Mitochondrial
keywords: Mitochondrial DNA; Mitochondrial function; Oxygen consumption