Egg activation: initiation and decoding of Ca2+signaling

Abstract

Introduction Egg activation refers to the early events that occur in the egg (or oocyte) that start embryo development. The most significant of these events in mammals is the resumption of meiosis, which is evident as the emission of a second polar body and then the formation of two polar bodies. However, egg activation in mammals also includes the exocytosis of cortical granules which leads to modifications of the zona pellucida, and changes in the pattern of protein and RNA synthesis. In mammals the sperm initiates the events of egg activation. Egg activation can also be initiated by various chemical and physical stimuli, and by modulating the activity of some key cell-cycle proteins. These artificial agents lead to egg activation in the absence of a sperm, which is termed parthenogenetic activation. We review the sequence and mechanism of egg activation in mammals, concentrating upon data in the mouse. Sperm-induced Ca 2+ oscillations The key change in the egg that initiates the events of egg activation is an increase in the cytosolic free Ca 2+ concentration. It was shown more than 25 years ago that fertilization of mouse and hamster eggs is associated with a series of cytosolic Ca 2+ oscillations [1, 2]. An example of such oscillations at fertilization in a mouse egg is shown in Figure 15.1. It can be seen that each Ca 2+ increase lasts about a minute but that there are repeated Ca 2+ transients that last for several hours. In mouse eggs these oscillations persist up until the time of the formation of pronuclei [3]. Similar Ca 2+ oscillations have now been reported in fertilizing eggs of a number of other different mammalian species such as pigs, cows, horse, rats, and humans. There are slight differences in the exact form of the Ca 2+ increase and in their frequency. In all cases the Ca 2+ spikes, or transient oscillations, are separated by at least 10 minutes, and the series as a whole lasts for several hours. In mouse eggs, the oscillations have been shown to be essential for the key events of activation since the introduction of Ca 2+ chelators into the cytosol blocks meiotic resumption and exocytosis [4]. Furthermore, we know these Ca 2+ increases are sufficient for egg activation because causing an artificial increase in intracellular Ca 2+ by applying a Ca 2+ ionophore, or by microinjecting Ca 2+ directly into the eggs, triggers development up to the blastocyst stage [1].