Phospholipase C zeta-1 (PLCZ1)

Phospholipase C zeta-1 (PLCZ1) is a sperm-specific enzyme that acts as the primary oocyte-activating factor required for successful monospermic fertilization in mammals. Upon sperm entry into the oocyte, PLCZ1 hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2) to produce inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). IP3 induces Ca⁺² release from the oocyte's endoplasmic reticulum, initiating a series of Ca⁺² oscillations critical for resuming the meiotic cell cycle and activating embryonic development. PLCZ1 consists of EF hand-like domains, X and Y catalytic domains, an XY-linker, and a C2 domain. Deficiency or mutations in PLCZ1 are linked to forms of male infertility associated with oocyte activation deficiency, and it is the basis for developing diagnostic and therapeutic interventions in assisted reproduction, such as mRNA/protein supplementation during ICSI. Its role is highly specific to fertilization; no approved drugs currently directly target PLCZ1, but its presence or absence serves as a biomarker for certain infertility diagnoses.

Other names

1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase zeta-1PLC-zeta-1NYD-SP27PLCzetaCzetaPhosphoinositide phospholipase C-zeta-1Testis-development protein NYD-SP27SPGF17PI-phospholipase C zeta 1testicular tissue protein Li 145testis-development related NYD-SP27

Hydrolysis of PIP2 in an oocyte after sperm entry, generating IP3 and DAG, triggering Ca⁺² release and downstream egg activation signaling. Restoration of oocyte activation via recombinant PLCZ1 or mRNA microinjection in cases of PLCZ1 deficiency.