Phospholipase C zeta and calcium oscillations at fertilisation: The evidence, applications, and further questions

Oocyte activation is a fundamental event at mammalian fertilisation, initiated by a series of characteristic calcium (Ca2+) oscillations in mammals. This characteristic pattern of Ca2+ release is induced in a species-specific manner by a sperm-specific enzyme termed phospholipase C zeta (PLCζ). Reduction or absence of functional PLCζ within sperm underlies male factor infertility in humans, due to mutational inactivation or abrogation of PLCζ protein expression. Underlying such clinical implications, a significant body of evidence has now been accumulated that has characterised the unique biochemical and biophysical properties of this enzyme, further aiding the unique clinical opportunities presented. Herein, we present and discuss evidence accrued over the past decade and a half that serves to support the identity of PLCζ as the mammalian sperm factor. Furthermore, we also discuss the potential novel avenues that have yet to be examined regarding PLCζ mechanism of action in both the oocyte, and the sperm. Finally, we discuss the advances that have been made regarding the clinical therapeutic and diagnostic applications of PLCζ in potentially treating male infertility as a result of oocyte activation deficiency (OAD), and also possibly more general cases of male subfertility.