PLC{zeta} is the physiological trigger of the Ca2+ oscillations that induce embryogenesis in mammals but conception can occur in its absence [RESEARCH ARTICLE]

Alaa Hachem, Jonathan Godwin, Margarida Ruas, Hoi Chang Lee, Minerva Ferrer Buitrago, Goli Ardestani, Andrew Bassett, Sebastian Fox, Felipe Navarrete, Petra de Sutter, Björn Heindryckx, Rafael Fissore, and John Parrington

Activation of the egg by the sperm is the first, vital stage of embryogenesis. The sperm protein PLC has been proposed as the physiological agent that triggers the Ca²⁺ oscillations that normally initiate embryogenesis. Consistent with this, recombinant PLC induces Ca²⁺ oscillations in eggs and debilitating mutations in the PLCZ1 gene are associated with infertility in men. However, there has been no evidence that knockout of the gene encoding PLC abolishes the ability of sperm to induce Ca²⁺ oscillations in eggs. Here, we show that sperm derived from Plcz1^–/– male mice fail to trigger Ca²⁺ oscillations in eggs, cause polyspermy and thus demonstrate that PLC is the physiological trigger of these Ca²⁺ oscillations. Remarkably, some eggs fertilized by PLC-null sperm can develop, albeit at greatly reduced efficiency, and after a significant time-delay. In addition, Plcz1^–/– males are subfertile but not sterile, suggesting that in the absence of PLC, spontaneous egg activation can eventually occur via an alternative route. This is the first demonstration that in vivo fertilization without the normal physiological trigger of egg activation can result in offspring. PLC-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.

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