The role and mechanism of action of sperm PLC-zeta in mammalian fertilisation

At mammalian fertilisation, the fundamental stimulus that triggers oocyte (egg) activation and initiation of early embryonic development is an acute rise of the intracellular-free calcium (Ca²⁺) concentration inside the egg cytoplasm. This essential Ca²⁺ increase comprises a characteristic series of repetitive Ca²⁺ oscillations, starting soon after sperm–egg fusion. Over the last 15 years, accumulating scientific and clinical evidence supports the notion that the physiological stimulus that precedes the cytosolic Ca²⁺ oscillations is a novel, testis-specific phospholipase C (PLC) isoform, known as PLC-zeta (PLCζ). Sperm PLCζ catalyses the hydrolysis of phosphatidylinositol 4,5-bisphosphate triggering cytosolic Ca²⁺ oscillations through the inositol 1,4,5-trisphosphate signalling pathway. PLCζ is the smallest known mammalian PLC isoform with the most elementary domain organisation. However, relative to somatic PLCs, the PLCζ isoform possesses a unique potency in stimulating Ca²⁺ oscillations in eggs that is attributed to its novel biochemical characteristics. In this review, we discuss the latest developments that have begun to unravel the vital role of PLCζ at mammalian fertilisation and decipher its unique mechanism of action within the fertilising egg. We also postulate the significant potential diagnostic and therapeutic capacity of PLCζ in alleviating certain types of male infertility.