Fertilization in the African clawed frog, Xenopus laevis, requires an egg-derived PLC to signal the fast block to polyspermy

Fertilization in <i>Xenopus laevis</i> triggers calcium release and membrane depolarization to activate the fast block to polyspermy. This depolarization requires phospholipase C (PLC) activity, but the identity and origin of the PLC remained unclear. We previously reported that <i>PLCZ1</i> , which encodes the sperm-derived PLCζ used in mammals and birds, was deleted in Pipidae frogs, suggesting an alternative mechanism. Here, we used the irreversible PLC inhibitor U73122 to test whether the PLC driving the fast block originates from the egg or sperm. Inhibiting PLC activity in the egg, but not in the sperm, abolished the fertilization-evoked depolarization and led to polyspermy. These findings demonstrate that <i>X. laevis</i> relies on an egg-derived PLC to signal the fast block, revealing a fertilization-triggered calcium signaling pathway that is mechanistically distinct from other vertebrates.