Schematic summary of the proposed mechanism underlying Ca2+ release at oocyte activation. The fertilizing sperm triggers Ca2+ following delivery of sperm-specific phospholipase C zeta (PLCζ) to the oolemma during or following oocyte-sperm membrane fusion. PLCζ interacts with an as yet unknown oocyte-borne factor(s), facilitating hydrolysis of PIP2 into DAG and InsP3, which subsequently triggers Ca2+ release from intracellular stores, alleviating the MII-arrest. The proposed mechanism mediates cortical granules exocytosis, MAPK deactivation and subsequent pronuclei formation and CaMKII activation, inhibiting CSF (Emi2) and liberating APC. This reduces levels of Cyclin B1 in the maturation-promoting factor (MPF) complex comprising CDK1 and Cyclin B1, which inactivates MPF, releasing the oocyte from MII-arrest. APC, anaphase-promoting complex/cyclosome; CaM/CaMKII, calcium/calmodulin-dependent protein kinase II; CSF, cytostatic factor; CNB1, cyclin B1; CDK1, cyclin-dependent kinase 1; DAG, diacylglycerol; InsP3, inositol 1,4,5-trisphosphate; InsP3R, InsP3 receptor; MAPK, mitogen-activated protein kinase; PIP2, phosphatidylinositol 4,5-bisphosphate; PKC, protein kinase C. Schematic reproduced with permission from Yeste et al. (2016b).