PLCζ is the Physiological Trigger of the Ca Oscillations That Induce Embryogenesis in Mammals but Conception Can Occur in Its Absence

Activation of the egg by the sperm is the first, vital stage of embryogenesis. The sperm protein PLCζ has been proposed as the physiological agent that triggers the Ca oscillations that normally initiate embryogenesis. Consistent with this, recombinant PLCζ induces Ca oscillations in eggs and debilitating mutations in the gene are associated with infertility in men. However, there has been no evidence that knockout of the gene encoding PLCζ abolishes the ability of sperm to induce Ca oscillations in eggs. Here, we show that sperm derived from male mice fail to trigger Ca oscillations in eggs, cause polyspermy and thus demonstrate that PLCζ is the physiological trigger of these Ca oscillations. Remarkably, some eggs fertilized by PLCζ-null sperm can develop, albeit at greatly reduced efficiency, and after a significant time-delay. In addition, males are subfertile but not sterile, suggesting that in the absence of PLCζ, spontaneous egg activation can eventually occur via an alternative route. This is the first demonstration that fertilization without the normal physiological trigger of egg activation can result in offspring. PLCζ-null sperm now make it possible to resolve long-standing questions in fertilization biology, and to test the efficacy and safety of procedures used to treat human infertility.