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.
Suzuki
Toru
T
RIKEN Center for Developmental Biology, Minamimachi, Chuo-ku, Kobe, Japan.
Yoshida
Naoko
N
Suzuki
Emi
E
Okuda
Erina
E
Perry
Anthony C F
AC
D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism*; D002614:Chelating Agents / Q000494:pharmacology; D005029:Ethylenediamines / Q000494:pharmacology; D005089:Exocytosis; D005260:Female; D008297:Male; D008677:Metaphase; D051379:Mice; D009865:Oocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D015032:Zinc / Q000378:metabolism*
D002614:Chelating Agents; D005029:Ethylenediamines; D046988:Proteasome Endopeptidase Complex; D015032:Zinc; C044387:N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine; D002118:Calcium