SPERM FACTORS AND EGG ACTIVATION: PLCzeta as the sperm factor that activates eggs: 20 years on.

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One of the simplest and most significant questions that we can ask about fertilization is: how does the sperm activate the egg? It has been known since the 1970s that sperm activate development of eggs by causing a transient increase in the cytosolic free Ca2+ ion concentration. These studies then shifted the question to one of how the sperm could cause the increases in Ca2+ in the egg. The publication of the discovery of phospholipase Czeta (PLCz) in August of 2002 was a critical moment in our understanding of mammalian egg activation (Saunders et al., 2002). This was because it identified PLCz as the protein in sperm extracts that could cause Ca2+ oscillations and mouse egg activation. It was the culmination of many years of searching to find the elusive soluble sperm factor that causes Ca2+ release in mammalian eggs. This factor is also often referred to as the ‘sperm-born oocyte activating factor’ or SOAF. Whilst some aspects of the search for sperm derived egg activating factors are not over, there can be little doubt that PLCz plays the central role in mammalian egg activation during in vitro fertilization and after the widely used technique of intracytoplasmic sperm injection (ICSI). It represents the first identified and foremost sperm derived egg activating factor.