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

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.