REPRODUCTIONRESEA CH Phospholipase Cz causes Ca21 oscillations and parthenogenetic activation of human oocytes

At fertilization in mammals the sperm activates development of the oocyte by inducing a prolonged series of oscillations in the cytosolic free Ca21 concentration. One theory of signal transduction at fertilization suggests that the sperm cause the Ca21 oscillations by introducing a protein factor into the oocyte after gamete membrane fusion. We recently identified this sperm-specific protein as phospholipase Cz (PLCz), and we showed that PLCz triggers Ca21 oscillations in unfertilized mouse oocytes. Here we report that microinjection of the complementary RNA for human PLCz causes prolonged Ca21 oscillations in aged human oocytes that had failed to fertilize during in vitro fertilization or intracytoplasmic sperm injection. The fre-quency of Ca21 oscillations was related to the concentration of complementary RNA injected. At low concentrations, PLCz stimulated parthenogenetic activation of oocytes. These embryos underwent cleavage divisions and some formed blastocysts. These data show that PLCz is a novel parthenogenetic stimulus for human oocytes and that it is unique in its ability to mimic the repetitive nature of the Ca21 stimulus provided by the sperm during human fertilization. Reproduction (2004) 128 697–70