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 (PLC zeta). Sperm PLC zeta catalyses the hydrolysis of phosphatidylinositol 4,5-bisphosphate triggering cytosolic Ca2+ oscillations through the inositol 1,4,5-trisphosphate signalling pathway. PLC zeta is the smallest known mammalian PLC isoform with the most elementary domain organisation. However, relative to somatic PLCs, the PLC zeta 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 PLC zeta 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 PLC zeta in alleviating certain types of male infertility.