PLCζ: a sperm-specific trigger of Ca2+ oscillations in eggs and embryo development

TLDR

Mammalian egg activation after fertilization depends on Ca²⁺ oscillations, yet the sperm‑derived trigger for this signaling remains unidentified. We identified sperm‑specific phospholipase Cζ (PLCζ) as the essential enzyme that initiates Ca²⁺ oscillations and is required for normal embryo development.

Abstract

Upon fertilisation by sperm, mammalian eggs are activated by a series of intracellular Ca2+ oscillations that are essential for embryo development. The mechanism by which sperm induces this complex signalling phenomenon is unknown. One proposal is that the sperm introduces an exclusive cytosolic factor into the egg that elicits serial Ca2+ release. The ‘sperm factor’ hypothesis has not been ratified because a sperm-specific protein that generates repetitive Ca2+ transients and egg activation has not been found. We identify a novel, sperm-specific phospholipase C, PLCζ, that triggers Ca2+ oscillations in mouse eggs indistinguishable from those at fertilisation. PLCζ removal from sperm extracts abolishes Ca2+ release in eggs. Moreover, the PLCζ content of a single sperm was sufficient to produce Ca2+ oscillations as well as normal embryo development to blastocyst. Our results are consistent with sperm PLCζ as the molecular trigger for development of a fertilised egg into an embryo.