title: A role for Aurora C in the chromosomal passenger complex during human preimplantation embryo development.
abstract: BACKGROUND
  Human embryos generated by IVF demonstrate a high incidence of chromosomal segregation errors during the cleavage divisions. To analyse underlying molecular mechanisms, we investigated the behaviour of the chromosomal passenger complex (CPC) in human oocytes and embryos. This important mitotic regulatory complex comprises the inner centromere protein (INCENP), survivin, borealin and Aurora B, or the meiotic kinase Aurora C.
  
  
  METHODS
  We analysed mRNA expression by quantitative RT-PCR of all CPC members in human oocytes, tripronuclear (3PN) zygotes, 2-cell and 4-cell embryos developed from 3PN zygotes, plus good-quality cryopreserved 8-cell, morula and blastocyst stage embryos. Protein expression and localization of CPC members were investigated by immunofluorescence in oocytes and embryos arrested at prometaphase. Histone H3S10 phosphorylation was investigated as an indicator of a functional CPC.
  
  
  RESULTS
  INCENP, survivin and borealin were detected at the inner centromere of prometaphase chromosomes in all stages investigated. Whereas Aurora B and C are both present in oocytes, Aurora C becomes the most prominent kinase in the CPC during the first three embryonic cell cycles. Moreover, Aurora C mRNA was up-regulated with Aurora B after activation of the embryonic genome and both proteins were detected in early Day 4 embryos. Subsequently, only Aurora B was detected in blastocysts.
  
  
  CONCLUSIONS
  In contrast to somatic cells, our results point to a specific role for Aurora C in the CPC during human preimplantation embryo development. Although, the presence of Aurora C in itself may not explain the high chromosome segregation error rate, the data presented here provide novel information regarding possible mechanisms.
authors.affiliation: Department of Reproductive Medicine and Gynaecology, University Medical Center Utrecht, Utrecht, The Netherlands. mavoribe@umcutrecht.nl
authors.forename: Margarida
authors.initials: M
authors.lastname: Avo Santos
authors.forename: Christine
authors.initials: C
authors.lastname: van de Werken
authors.forename: Marieke
authors.initials: M
authors.lastname: de Vries
authors.forename: Holger
authors.initials: H
authors.lastname: Jahr
authors.forename: Martijn J M
authors.initials: MJ
authors.lastname: Vromans
authors.forename: Joop S E
authors.initials: JS
authors.lastname: Laven
authors.forename: Bart C
authors.initials: BC
authors.lastname: Fauser
authors.forename: Geert J
authors.initials: GJ
authors.lastname: Kops
authors.forename: Susanne M
authors.initials: SM
authors.lastname: Lens
authors.forename: Esther B
authors.initials: EB
authors.lastname: Baart
mesh_terms: D064107:Aurora Kinase B; D064108:Aurora Kinase C; D064127:Aurora Kinases; D001755:Blastocyst / Q000201:enzymology* / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000032:analysis / Q000378:metabolism; D002503:Centromere / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000032:analysis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020090:Chromosome Segregation / Q000502:physiology; D047108:Embryonic Development / Q000235:genetics*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000032:analysis / Q000378:metabolism; D008297:Male; D009865:Oocytes / Q000201:enzymology / Q000378:metabolism; D011247:Pregnancy; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D013090:Spermatocytes / Q000201:enzymology; D000077022:Survivin
chemical_list: C107489:BIRC5 protein, human; C490157:CDCA8 protein, human; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; C083767:INCENP protein, human; D051034:Inhibitor of Apoptosis Proteins; D012333:RNA, Messenger; D000077022:Survivin; C576921:AURKB protein, human; C576927:AURKC protein, human; D064107:Aurora Kinase B; D064108:Aurora Kinase C; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases