Resumen de Oscillatory Ca2+ dynamics and cell cycle resumption at fertilization in mammals: a modelling approach
Geneviève Dupont, Elke Heytens, Luc Leybaert
Fertilization in mammals is accompanied by Ca2+ oscillations in the egg cytoplasm, leading to exit from meiosis and entry into the first embryonic cell cycle. The signal transduction pathway linking these Ca2+ changes to cell-cycle related kinases has not yet been fully elucidated, but involves activation of calmodulin-dependent kinase II (CaMKII). Here, we develop a computational model to investigate the mechanism by which cell cycle resumption can be sensitive to the temporal pattern of Ca2+ increases. Using a model for CaMKII activation that reproduces the frequency sensitivity of this kinase, simulations confirm that Ca2+ spikes are accompanied by in phase variations in the level of CaMKII activity and suggest that in most mammalian species, Ca2+ spikes are well suited to maximize CaMKII activation. The full model assumes that CaMKII brings about a decrease in the level of cyclinB-cdk1 by two pathways, only one of which is CSF-dependent. Parameters are selected to account for the experimental observations where mouse eggs were artificially activated by different Ca2+ stimulatory protocols. The model is then used in the context of �assisted oocyte activation (AOA)� to investigate why the best rates of successful activation are obtained when eggs are submitted to two applications of Ca2+ ionophores.
