Zinc maintains prophase i arrest in mouse oocytes through regulation of the: Mos-mapk pathway

Betty Y. Kong, Miranda L. Bernhardt, Alison M. Kim, Thomas V. O'Halloran, Teresa K. Woodruff*

*Corresponding author for this work

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

Meiosis in mammalian females is marked by two arrest points, at prophase I and metaphase II, which must be tightly regulated in order to produce a haploid gamete at the time of fertilization. The transition metal zinc has emerged as a necessary and dynamic regulator of the establishment, maintenance, and exit from metaphase II arrest, but the roles of zinc during prophase I arrest are largely unknown. In this study, we investigate the mechanisms of zinc regulation during the first meiotic arrest. Disrupting zinc availability in the prophase I arrested oocyte by treatment with the heavy metal chelator N,N,N′,N′-tetrakis-(2-pyridylmethyl)-ethylenediamine (TPEN) causes meiotic resumption even in the presence of pharmacological inhibitors of meiosis. We further show that the MOS-MAPK pathway mediates zinc-dependent prophase I arrest, as the pathway prematurely activates during TPEN-induced meiotic resumption. Conversely, inhibition of the MOS-MAPK pathway maintains prophase I arrest. While prolonged zinc insufficiency ultimately results in telophase I arrest, early and transient exposure of oocytes to TPEN is sufficient to induce meiotic resumption and bypass the telophase I block, allowing the formation of developmentally competent eggs upon parthenogenetic activation. These results establish zinc as a crucial regulator of meiosis throughout the entirety of oocyte maturation, including the maintenance of and release from the first and second meiotic arrest points.

Original languageEnglish (US)
Pages (from-to)11
Number of pages1
JournalBiology of reproduction
Volume87
Issue number1
DOIs
StatePublished - Jul 2012

Keywords

  • Egg
  • MAPK
  • MOS
  • Meiosis
  • Oocyte
  • Zinc

ASJC Scopus subject areas

  • Reproductive Medicine
  • Cell Biology

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