Zn is essential for Ca oscillations in mouse eggs.

Changes in the intracellular concentration of free calcium (Ca) underpin egg activation and initiation of development in animals and plants. In mammals, the Ca release is periodical, known as Ca oscillations, and mediated by the type 1 inositol 1,4,5-trisphosphate receptor (IPR1). Another divalent cation, zinc (Zn), increases exponentially during oocyte maturation and is vital for meiotic transitions, arrests, and polyspermy prevention. It is unknown if these pivotal cations interplay during fertilization. Here, using mouse eggs, we showed that basal concentrations of labile Zn are indispensable for sperm-initiated Ca oscillations because Zn-deficient conditions induced by cell-permeable chelators abrogated Ca responses evoked by fertilization and other physiological and pharmacological agonists. We also found that chemically or genetically generated eggs with lower levels of labile Zn displayed reduced IPR1 sensitivity and diminished ER Ca leak despite the stable content of the stores and IPR1 mass. Resupplying Zn restarted Ca oscillations, but excessive Zn prevented and terminated them, hindering IPR1 responsiveness. The findings suggest that a window of Zn concentrations is required for Ca responses and IPR1 function in eggs, ensuring optimal response to fertilization and egg activation.