title: The inorganic anatomy of the mammalian preimplantation embryo and the requirement of zinc during the first mitotic divisions.
abstract: BACKGROUND
  Zinc is the most abundant transition metal in the mammalian oocyte, and dynamic fluxes in intracellular concentration are essential for regulating both meiotic progression and fertilization. Whether the defined pathways of zinc utilization in female meiosis directly translate to mitotic cells, including the mammalian preimplantation embryo, has not been studied previously.
  
  
  RESULTS
  We determined that zinc is the most abundant transition metal in the preimplantation embryo, with levels an order of magnitude higher than those of iron or copper. Using a zinc-specific fluorescent probe, we demonstrated that labile zinc is distributed in vesicle-like structures in the cortex of cells at all stages of preimplantation embryo development. To test the importance of zinc during this period, we induced zinc insufficiency using the heavy metal chelator N,N,N',N'-tetrakis-(2-pyridylmethyl)-ethylenediamine (TPEN). Incubation of embryos in media containing TPEN resulted in a developmental arrest that was specific to zinc chelation and associated with compromised mitotic parameters. The developmental arrest due to zinc insufficiency was associated with altered chromatin structure in the blastomere nuclei and decreased global transcription.
  
  
  CONCLUSIONS
  These results demonstrate for the first time that the preimplantation embryo requires tight zinc regulation and homeostasis for the initial mitotic divisions of life.
authors.affiliation: Department of Obstetrics and Gynecology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Betty Y
authors.initials: BY
authors.lastname: Kong
authors.affiliation: Department of Obstetrics and Gynecology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Francesca E
authors.initials: FE
authors.lastname: Duncan
authors.affiliation: Department of Chemistry, Northwestern University, Evanston, Illinois.
authors.forename: Emily L
authors.initials: EL
authors.lastname: Que
authors.affiliation: Department of Obstetrics and Gynecology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Yuanming
authors.initials: Y
authors.lastname: Xu
authors.affiliation: X-ray Science Division, Argonne National Laboratory, Argonne, Illinois.
authors.forename: Stefan
authors.initials: S
authors.lastname: Vogt
authors.affiliation: Department of Chemistry, Northwestern University, Evanston, Illinois.|Department of Molecular Biosciences, Evanston, Illinois.
authors.forename: Thomas V
authors.initials: TV
authors.lastname: O'Halloran
authors.affiliation: Department of Obstetrics and Gynecology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois.|Department of Molecular Biosciences, Evanston, Illinois.
authors.forename: Teresa K
authors.initials: TK
authors.lastname: Woodruff
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000187:drug effects / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000187:drug effects / Q000378:metabolism*; D005029:Ethylenediamines / Q000494:pharmacology; D005260:Female; D051379:Mice; D008856:Microscopy, Fluorescence; D008938:Mitosis / Q000187:drug effects; D011247:Pregnancy; D015032:Zinc / Q000378:metabolism*
chemical_list: D005029:Ethylenediamines; D015032:Zinc; C044387:N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine
keywords: mitosis; preimplantation embryo; zinc