Signalling mechanisms of mammalian oocyte activation

Abstract Oocyte activation occurs at the time of fertilization and is a series of cellular events initiated by intracellular Ca2+ increases. Consequently, oocytes are alleviated from their arrested state in meiotic metaphase II (MII), allowing for the completion of meiosis. Oocyte activation is also an essential step for somatic cell nuclear transfer (SCNT) and an important tool to overcome clinical infertility. Traditional artificial activation methods aim to mimic the intracellular Ca2+ changes which occur during fertilization. Recent studies emphasize the importance of cytoplasmic Zn2+ on oocyte maturation and the completion of meiosis, thus suggesting artificial oocyte activation approaches that are centered around the concentration of available Zn2+in oocytes. Depletion of intracellular Zn2+ in oocytes with heavy metal chelators leads to successful oocyte activation in the absence of cellular Ca2+ changes, indicating that successful oocyte activation does not always depends on intracellular Ca2+ increases. Current findings lead to new approaches to artificially activate mammalian oocytes by reducing available Zn2+ contents, and the approaches improve the outcome of oocyte activation when combined with existing Ca2+ based oocyte activation methods. Here, we review the important role of Ca2+ and Zn2+ in mammalian oocyte activation and development of novel oocyte activation approaches based on Zn2+ availability.

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Noninvasive imaging of spindle dynamics during mammalian oocyte activation

Fertility and Sterility ◽

10.1016/j.fertnstert.2004.07.983 ◽

2005 ◽

Vol 83 (4) ◽

pp. 1197-1205 ◽

Cited By ~ 29

Author(s):

P NAVARRO ◽

L LIU ◽

J TRIMARCHI ◽

R FERRIANI ◽

D KEEFE

Keyword(s):

Noninvasive Imaging ◽

Oocyte Activation ◽

Mammalian Oocyte ◽

Spindle Dynamics

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Sperm phospholipase Czeta from humans and cynomolgus monkeys triggers Ca2+ oscillations, activation and development of mouse oocytes

Reproduction ◽

10.1530/rep.0.1240611 ◽

2002 ◽

pp. 611-623 ◽

Cited By ~ 188

Author(s):

LJ Cox ◽

MG Larman ◽

CM Saunders ◽

K Hashimoto ◽

K Swann ◽

...

Keyword(s):

Cynomolgus Monkey ◽

Mammalian Species ◽

Blastocyst Stage ◽

Egg Activation ◽

Oocyte Activation ◽

Cynomolgus Monkeys ◽

Mammalian Oocyte ◽

Mouse Oocytes ◽

Sperm Factor ◽

Mouse Egg

Fusion with a fertilizing spermatozoon induces the mammalian oocyte to undergo a remarkable series of oscillations in cytosolic Ca(2+), leading to oocyte activation and development of the embryo. The exact molecular mechanism for generating Ca(2+) oscillations has not been established. A sperm-specific zeta isoform of phospholipase C (PLCzeta) has been identified in mice. Mouse PLCzeta triggers Ca(2+) oscillations in mouse oocytes and exhibits properties synonymous with the 'sperm factor' that has been proposed to diffuse into the oocyte after gamete fusion. The present study isolated the PLCzeta homologue from human and cynomolgus monkey testes. Comparison with mouse and monkey PLCzeta protein sequences indicates a shorter X-Y linker region in human PLCzeta and predicts a distinctly different isoelectric point. Microinjection of complementary RNA for both human and cynomolgus monkey PLCzeta elicits Ca(2+) oscillations in mouse oocytes equivalent to those seen during fertilization in mice. Moreover, human PLCzeta elicits mouse egg activation and early embryonic development up to the blastocyst stage, and exhibits greater potency than PLCzeta from monkeys and mice. These results are consistent with the proposal that sperm PLCzeta is the molecular trigger for egg activation during fertilization and that the role and activity of PLCzeta is highly conserved across mammalian species.

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Mammalian Oocyte Activation by the Synergistic Action of Discrete Sperm Head Components: Induction of Calcium Transients and Involvement of Proteolysis

Developmental Biology ◽

10.1006/dbio.1999.9552 ◽

2000 ◽

Vol 217 (2) ◽

pp. 386-393 ◽

Cited By ~ 52

Author(s):

Anthony C.F. Perry ◽

Teruhiko Wakayama ◽

Ian M. Cooke ◽

Ryuzo Yanagimachi

Keyword(s):

Sperm Head ◽

Synergistic Action ◽

Calcium Transients ◽

Oocyte Activation ◽

Mammalian Oocyte

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Role Of Stim1 And Orai1 In Mammalian Oocyte Activation

10.5339/qfarc.2014.hbpp0176 ◽

2014 ◽

Author(s):

Satanay Hubrack ◽

Ethel Adap ◽

Stefan Feske ◽

Khaled Machaca

Keyword(s):

Oocyte Activation ◽

Mammalian Oocyte

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Single Ca2+ transients vs oscillatory Ca2+ signaling for assisted oocyte activation: limitations and benefits

Reproduction ◽

10.1530/rep-17-0098 ◽

2018 ◽

Vol 155 (2) ◽

pp. R105-R119 ◽

Cited By ~ 13

Author(s):

Minerva Ferrer-Buitrago ◽

Davina Bonte ◽

Petra De Sutter ◽

Luc Leybaert ◽

Björn Heindryckx

Keyword(s):

Embryonic Development ◽

Oocyte Activation ◽

Frequency Pattern ◽

Meiotic Progression ◽

Assisted Reproduction Technology ◽

Mammalian Oocyte ◽

Cellular Events ◽

Specific Frequency ◽

Species Specific ◽

Assisted Oocyte Activation

Oocyte activation is a calcium (Ca2+)-dependent process that has been investigated in depth, in particular, regarding its impact on assisted reproduction technology (ART). Following a standard model of signal transduction, Ca2+drives the meiotic progression upon fertilization in all species studied to date. However, Ca2+changes during oocyte activation are species specific, and they can be classified in two modalities based on the pattern defined by the Ca2+signature: a single Ca2+transient (e.g. amphibians) or repetitive Ca2+transients called Ca2+oscillations (e.g. mammals). Interestingly, assisted oocyte activation (AOA) methods have highlighted the ability of mammalian oocytes to respond to single Ca2+transients with normal embryonic development. In this regard, there is evidence supporting that cellular events during the process of oocyte activation are initiated by different number of Ca2+oscillations. Moreover, it was proposed that oocyte activation and subsequent embryonic development are dependent on the total summation of the Ca2+peaks, rather than to a specific frequency pattern of Ca2+oscillations. The present review aims to demonstrate the complexity of mammalian oocyte activation by describing the series of Ca2+-linked physiological events involved in mediating the egg-to-embryo transition. Furthermore, mechanisms of AOA and the limitations and benefits associated with the application of different activation agents are discussed.

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