Oocyte activation occurs at the time of fertilization and is a series of cellular events initiated by intracellular Ca²⁺ increases. Consequently, oocytes are alleviated from their arrested state in meiotic metaphase II (MII), allowing for the completion of meiosis. Oocyte activation is also an essential step for somatic cell nuclear transfer and an important tool to overcome clinical infertility. Traditional artificial activation methods aim to mimic the intracellular Ca²⁺ changes which occur during fertilization. Recent studies emphasize the importance of cytoplasmic Zn²⁺ on oocyte maturation and the completion of meiosis, thus suggesting artificial oocyte activation approaches that are centered around the concentration of available Zn²⁺ in oocytes. Depletion of intracellular Zn²⁺ in oocytes with heavy metal chelators leads to successful oocyte activation in the absence of cellular Ca²⁺ changes, indicating that successful oocyte activation does not always depends on intracellular Ca²⁺ increases. Current findings lead to new approaches to artificially activate mammalian oocytes by reducing available Zn²⁺ contents, and the approaches improve the outcome of oocyte activation when combined with existing Ca²⁺-based oocyte activation methods. Here, we review the important role of Ca²+ and Zn²⁺ in mammalian oocyte activation and development of novel oocyte activation approaches based on Zn²⁺ availability.

Summary Sentence Artificial oocyte activation is essential for the application of Assisted Reproductive Technology and the ability to control the level of cytoplasmic zinc can facilitate oocyte activation process.