Fertilization is a critical process in sexual reproduction that involves the fusion of a capacitated sperm with a mature oocyte to form a zygote. Polyspermy, the fertilization of an oocyte by multiple sperm, leads to polyploidy and embryo lethality. Mammalian and non-mammalian oocytes have evolved mechanisms to prevent polyspermy, including fast and slow blocks. The fast block comprises membrane depolarization post-sperm fusion, temporarily preventing additional sperm fusion. The slow block, triggered by cortical granule (CG) exocytosis, involves the release of proteins that modify the