Molecular Mechanism of Oocyte Activation in Mammals: Past, Present, and Future Directions

During mammalian fertilization, repetitive intracellular Ca²⁺ increases known as Ca²⁺ oscillations occur. These oscillations are considered crucial for successful fertilization and subsequent embryonic development. Numerous researchers have endeavored to elucidate the factors responsible for inducing Ca²⁺ oscillations across various mammalian species. Notably, sperm-specific phospholipase C zeta (PLCζ) emerged as a prominent candidate capable of initiating Ca²⁺ oscillations, particularly in mammals. Genetic mutation of PLCζ in humans results in the absence of Ca²⁺ oscillations in mouse oocytes. Recent studies further underscored PLCζ's significance, revealing that sperm from PLCζ-deficient (Plcz1^-/-) mice fail to induce Ca²⁺ oscillations upon intracytoplasmic sperm injection (ICSI). Despite these findings, observations from in vitro fertilization (IVF) experiments using Plcz1^-/- sperm revealed some residual intracellular Ca²⁺ increases and successful oocyte activation, hinting at potential alternative mechanisms. In this review, we introduced the current hypothesis surrounding oocyte activation in mammals, informed by contemporary literature, and probed into the enigmatic mechanisms underlying mammalian fertilization-induced oocyte activation.