Figure 11.

Proposed two-factor mechanism of sperm-induced oocyte activation. The sperm oocyte-activating factor (SOAF) is released from the PAS region of the sperm head PT into the ooplasm upon sperm–oocyte fusion. The two candidate SOAF proteins, PLCZ1 and WBP2NL/WBP2 would facilitate the hydrolysis of PIP₂ to IP_3. Next, IP₃ would bind to the IP₃R receptor on the endoplasmic reticulum (ER), and trigger the release of Ca²⁺ from its stores, ultimately increasing the intracellular Ca²⁺ in the oocyte cytosol. This mechanism would be activated either directly, in the case of PLCZ1, or indirectly in the case of WBP2NL/WBP2. It is proposed that WBP2NL/WBP2 would bind to the ooplasmic WWI domain containing proteins to activate oocyte PLC Gamma (PLCG), catalyzing the hydrolysis of PIP₂ to IP₃. The increase in Ca²⁺ would result in the downstream activation of enzymes such as the calcium-calmodulin kinase (CAMK) and the anaphase promoting complex (APC) catalyzing the completion of oocyte meiosis and further, repetitive Ca²⁺-induced Ca²⁺ release (Ca²⁺ oscillations). Additionally, WBP2NL/WBP2 may aid in the regulation and/or activation of WWI domain containing proteins shown to have roles in the early stages of zygotic development after the initial activation of the oocyte. Specifically, WBP2/WBP2NL could serve as adaptors of yet to be identified transcription factors responsible for the minor zygotic genome activation, resulting in transcription of a small number of genes in the pronuclei, observed in mammalian zygotes.