Calcium oscillations in mammalian eggs triggered by a soluble sperm protein

Abstract

AT fertilization in mammals, the sperm induces a characteristic series of Ca²⁺ oscillations in the egg which serve as the essential trigger for egg activation and early development of the embryo^1–3. It is not known how the sperm initiates this fundamental process, however^4–6, nor has any pathway linking sperm–egg membrane-receptor binding with intracellular Ca²⁺ release been demonstrated^7–11. Microinjection of sperm extracts into mammalian eggs elicits Ca²⁺ oscillations identical to those occurring at fertilization^12–14, which suggests that sperm may introduce a Ca²⁺ oscillation-inducing factor into the egg on gamete membrane fusion^12,15–18. Here we identify a soluble sperm protein that exhibits Ca²⁺ oscillation-inducing ('oscillogen') activity in eggs. Sperm oscillogen exists as an oligomer with a subunit of M_r 33K and a specific intracellular localization at the equatorial segment of the sperm head. Cloning of the 33K oscillogen complementary DNA indicates similarity with a hexose phosphate isomerase found in prokaryotes. This sperm-derived oscillogen, termed oscillin, may represent the physiological trigger for development in mammals.