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After receiving the LH surge, a mature oocyte (egg) is collected in the oviduct of mammalian females. Following fusion of the gametes, the sperm elicits in the egg repeated calcium (Ca 2 + ) transients known as oscillations, which trigger egg activation. Completion of egg activation renders the meiotic and transcriptionally silent egg into a mitotically competent, transcriptionally active zygote that eventually undergoes cell differentiation and embryo development. Here, we discuss the major events of egg activation and the molecular players that underlie them. We describe the universal role of Ca 2 + on egg activation as well as the egg's Ca 2 + toolkit. We explain how failure of egg activation results in infertility, and the value of ICSI and genetic models in identifying the molecular causes of this infertility. Finally, we point to areas where additional research is needed and how this knowledge will allow better control of fertility.

Since the birth of the first cloned sheep, “Dolly”, many studies have reported the successful use of cloning by somatic cell nuclear transfer in other mammalian species. In spite of these successes, the efficiency of this technique is low, with less than 10% of generated embryos resulting in offspring. Factors of genetic, epigenetic, and technical origin seem to affect the efficiency of cloning. Further, because these reconstructed embryos do not have the benefit of being activated by the sperm, egg activation relies on artificial procedures such as those delivered by chemical or physical stimuli. In general, these stimuli aim to replicate either the signal delivered by the sperm, namely, elevations in the intracellular concentration of calcium ion ([Ca2+]i), or the outcome of this signal, inactivation of the M-phase kinases that are responsible for the metaphase II arrest. In mammalian fertilization, the sperm initiates repetitive increases in [Ca2+]i that are also known as oscillations, and experimentally replicating these oscillations has been difficult to accomplish, except in mouse eggs where oscillations can be attained by replacing extracellular CaCl2 with SrCl2. In other mammalian species, in the absence of oscillations, most activation protocols incorporate chemical methods to subdue the activity of the M-phase kinases. Here, we will briefly describe oocyte activation protocols presently in use in different species, highlight some of their advantages and disadvantages, and discuss possible improvements.

Publisher Summary Mammalian oocytes are ovulated arrested at the metaphasic stage of the second meiotic division (MII), from which they initiate the embryonic development if fertilized in a timely manner. Prior to the MII arrest, the oocytes undergo maturation, during which they progress from the G2/M stage of the first meiotic division to MII. During this process, the oocytes undergo significant reorganization and redistribution of organelles and acquire a full complement of signaling molecules. These changes render the mammalian oocytes competent to exit meiosis and initiate embryonic development. Exit from the MII arrest is accomplished by fertilization, and is commonly referred to as “oocyte activation.” Oocyte activation comprises a sequence of cellular changes, all of which have to be completed to assure the development to the term. Oocyte activation is triggered by Ca2+ release, and in mammalian oocytes, multiple [Ca2+]i oscillations are required to achieve full activation. This chapter focuses on the Ca2+ requirements of mammalian oocytes necessary to initiate activation and development, and compares the mechanisms of action of the various parthenogenetic procedures. The probable pathway(s) by which the sperm may initiate Ca2+ release and the mechanism(s) that may control the persistence and termination of oscillations are also reviewed. The cellular and molecular events required for a pronuclear assembly as well as the likely differences in the assembly and composition of nuclear envelope membranes formed following the transfer of a somatic nucleus and their impact on the embryo development are discussed. Finally, recent evidence suggesting a role for [Ca2+]i oscillations as an apoptotic-inducing agent, rather than an activating agent, is examined.