Oocyte activation and phospholipase C zeta (PLC): Male infertility and implications for therapeutic intervention

Infertility is a condition that now affects an estimated one in seven couples. In approximately 40 % of cases, the primary cause of infertility rests with male-derived factors associated with a variety of anatomical, physiological, and molecular deficiencies. In a proportion of such cases, the functional ability of sperm to successfully fertilise and activate the oocyte is compromised. While assisted reproductive technology can successfully circumvent some of these issues via the application of artificial oocyte-activating agents, there is significant ongoing debate as to whether these chemical agents should be replaced with an endogenous alternative. Phospholipase C zeta (PLCZ) is the sperm-specific protein responsible for activating the quiescent oocyte following gamete fusion. Identified in a number of mammalian and non-mammalian organisms, PLCZ plays a fundamental role in the process of oocyte activation by inducing the controlled release of calcium in the ooplasm via an inositol triphosphate (IP3)-mediated signalling cascade. A growing body of evidence shows clear association between abnormalities in PLCZ structure, expression, localisation, and function to characterised states of human male infertility. Consequently there is significant global interest in PLCZ as both an endogenous therapeutic target to rescue infertile states associated with PLCZ-linked oocyte activation deficiency, and a diagnostic marker for oocyte activation ability. Here, we discuss the present status of PLCZ research and contemplate future applications of this fundamental sperm PLC in the clinic.