Sperm phospholipase Cζ from humans and cynomoigus monkeys triggers Ca2+ oscillations, activation and development of mouse oocytes

Fusion with a fertilizing spermatozoon induces the mammalian oocyte to undergo a remarkable series of oscillations in cytosolic Ca2+, leading to oocyte activation and development of the embryo. The exact molecular mechanism for generating Ca2+ oscillations has not been established. A sperm-specific zeta isoform of phospholipase C (PLC.) has been identified in mice. Mouse PLC triggers Ca2+ oscillations in mouse oocytes and exhibits properties synonymous with the 'sperm factor' that has been proposed to diffuse into the oocyte after gamete fusion. The present study isolated the PLC homologue from human and cynomolgus monkey testes. Comparison with mouse and monkey PLC protein sequences indicates a shorter X-Y linker region in human PLCzeta and predicts a distinctly different isoelectric point. Microinjection of complementary RNA for both human and cynomolgus monkey PLC elicits Ca2+ oscillations in mouse oocytes equivalent to those seen during fertilization in mice. Moreover, human PLCzeta elicits mouse egg activation and early embryonic development up to the blastocyst stage, and exhibits greater potency than PLCzeta from monkeys and mice. These results are consistent with the proposal that sperm PLCzeta is the molecular trigger for egg activation during fertilization and that the role and activity of PLCzeta is highly conserved across mammalian species.