title: Maternally-derived zinc transporters ZIP6 and ZIP10 drive the mammalian oocyte-to-egg transition.
abstract: Rapid cellular zinc influx regulates early mammalian development during the oocyte-to-egg transition through modulation of the meiotic cell cycle. Despite the physiological necessity of this zinc influx, the molecular mechanisms that govern such accumulation are unknown. Here we show that the fully grown mammalian oocyte does not employ a transcriptionally based mechanism of zinc regulation involving metal response element-binding transcription factor-1 (MTF-1), as demonstrated by a lack of MTF-1 responsiveness to environmental zinc manipulation. Instead, the mammalian oocyte controls zinc uptake through two maternally derived and cortically distributed zinc transporters, ZIP6 and ZIP10. Targeted disruption of these transporters using several approaches during meiotic maturation perturbs the intracellular zinc quota and results in a cell cycle arrest at a telophase I-like state. This arrest phenocopies established models of zinc insufficiency during the oocyte-to-egg transition, indicating the essential function of these maternally expressed transporters. Labile zinc localizes to punctate cytoplasmic structures in the human oocyte, and ZIP6 and ZIP10 are enriched in the cortex. Altogether, we demonstrate a mechanism of metal regulation required for female gamete development that may be evolutionarily conserved.
authors.affiliation: Department of Obstetrics and Gynecology, Northwestern University, Feinberg School of Medicine, 250 East Superior Street, Suite 3-2303, Chicago, IL 60611, USA.
authors.forename: B Y
authors.initials: BY
authors.lastname: Kong
authors.affiliation: Department of Obstetrics and Gynecology, Northwestern University, Feinberg School of Medicine, 250 East Superior Street, Suite 3-2303, Chicago, IL 60611, USA.
authors.forename: F E
authors.initials: FE
authors.lastname: Duncan
authors.affiliation: The Chemistry of Life Processes Institute and Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208, USA.
authors.forename: E L
authors.initials: EL
authors.lastname: Que
authors.affiliation: Department of Obstetrics and Gynecology, Northwestern University, Feinberg School of Medicine, 250 East Superior Street, Suite 3-2303, Chicago, IL 60611, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Kim
authors.affiliation: The Chemistry of Life Processes Institute and Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208, USA Department of Molecular Biosciences, Northwestern University, 2205 Tech Drive, Hogan 2-100, Evanston, IL 60208, USA t-ohalloran@northwestern.edu tkw@northwestern.edu.
authors.forename: T V
authors.initials: TV
authors.lastname: O'Halloran
authors.affiliation: Department of Obstetrics and Gynecology, Northwestern University, Feinberg School of Medicine, 250 East Superior Street, Suite 3-2303, Chicago, IL 60611, USA Department of Molecular Biosciences, Northwestern University, 2205 Tech Drive, Hogan 2-100, Evanston, IL 60208, USA t-ohalloran@northwestern.edu tkw@northwestern.edu.
authors.forename: T K
authors.initials: TK
authors.lastname: Woodruff
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D001692:Biological Transport / Q000235:genetics; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002453:Cell Cycle / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D006706:Homeostasis; D006801:Humans; D008815:Mice, Inbred Strains; D009865:Oocytes / Q000378:metabolism; D020218:Response Elements; D013692:Telophase; D015032:Zinc / Q000378:metabolism*
chemical_list: D027682:Cation Transport Proteins; C454113:Slc39a6 protein, mouse; C557566:ZIP10 protein, mouse; D015032:Zinc
keywords: human; meiosis; oocyte; zinc; zinc transporters