Sperm-Induced Ca²⁺ Release in Mammalian Eggs: The Roles of PLCζ, InsP₃, and ATP

Mammalian egg activation at fertilization is triggered by a long-lasting series of increases in cytosolic Ca²⁺ concentration. These Ca²⁺ oscillations are due to the production of InsP₃ within the egg and the subsequent release of Ca²⁺ from the endoplasmic reticulum into the cytosol. The generation of InsP₃ is initiated by the diffusion of sperm-specific phospholipase Czeta1 (PLCζ) into the egg after gamete fusion. PLCζ enables a positive feedback loop of InsP₃ production and Ca²⁺ release which then stimulates further InsP₃ production. Most cytosolic Ca²⁺ increases in eggs at fertilization involve a fast Ca²⁺ wave; however, due to the limited diffusion of InsP₃, this means that InsP₃ must be generated from an intracellular source rather than at the plasma membrane. All mammalian eggs studied generated Ca²⁺ oscillations in response to PLCζ, but the sensitivity of eggs to PLCζ and to some other stimuli varies between species. This is illustrated by the finding that incubation in Sr²⁺ medium stimulates Ca²⁺ oscillations in mouse and rat eggs but not eggs from other mammalian species. This difference appears to be due to the sensitivity of the type 1 InsP₃ receptor (IP3R1). I suggest that ATP production from mitochondria modulates the sensitivity of the IP3R1 in a manner that could account for the differential sensitivity of eggs to stimuli that generate Ca²⁺ oscillations.