Full-term mouse development by abolishing Zn2+-dependent metaphase II arrest without Ca2+ release

Development. 2010 Aug;137(16):2659-69. doi: 10.1242/dev.049791. Epub 2010 Jun 30.

Abstract

In vertebrates, a rise in intracellular free Ca(2+) (Ca(2+)(i)) levels during fertilization initiates second metaphase (mII) exit and the developmental programme. The Ca(2+) rise has long been considered to be crucial for development, but verifying this contribution would benefit from defining its role during fertilization. Here, we delineate the role of Ca(2+) release during mII exit in wild-type mouse eggs and show that it is dispensable for full-term development. Exit from mII can be induced by Zn(2+)-specific sequestration without Ca(2+) release, eliciting Cyclin B degradation in a manner dependent upon the proteasome pathway and intact microtubules, but not accompanied by degradation of the meiotic regulator Emi2. Parthenogenotes generated by Zn(2+) sequestration developed in vitro with normal expression of Ca(2+)-sensitive genes. Meiotic exit induced by either Ca(2+) oscillations or a single Ca(2+) rise in oocytes containing a signaling-deficient sperm resulted in comparable developmental rates. In the absence of Ca(2+) release, full-term development occurred approximately 50% less efficiently, but at readily detectable rates, with the birth of 27 offspring. These results show in intact mouse oocytes that Zn(2+) is essential for mII arrest and suggest that triggering meiotic exit is the sole indispensable developmental role of Ca(2+) signaling in mammalian fertilization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Calcium / metabolism*
  • Chelating Agents / pharmacology
  • Ethylenediamines / pharmacology
  • Exocytosis
  • Female
  • Male
  • Metaphase*
  • Mice
  • Oocytes / cytology
  • Oocytes / drug effects
  • Oocytes / metabolism
  • Proteasome Endopeptidase Complex / metabolism
  • Zinc / metabolism*

Substances

  • Chelating Agents
  • Ethylenediamines
  • Proteasome Endopeptidase Complex
  • Zinc
  • N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine
  • Calcium