scholarly journals The soluble sperm factor that activates the egg: PLCzeta and beyond

Reproduction ◽  
2020 ◽  
Vol 160 (1) ◽  
pp. V9-V11
Author(s):  
Karl Swann
Keyword(s):  
Egg Activation ◽  
Sperm Factor ◽  
Mouse Eggs

PLCzeta(ζ) initiates Ca2+ oscillations and egg activation at fertilization in mammals, but studies in mouse eggs fertilized by PLCζ knockout (KO) sperm imply that there is another slow acting factor causing Ca2+ release. Here, I propose a hypothesis for how this second sperm factor might cause Ca2+ oscillations in mouse eggs.

PLCζ: a sperm-specific trigger of Ca2+ oscillations in eggs and embryo development

Development ◽  
2002 ◽  
Vol 129 (15) ◽  
pp. 3533-3544 ◽  
Author(s):  
Christopher M. Saunders ◽  
Mark G. Larman ◽  
John Parrington ◽  
Llewellyn J. Cox ◽  
Jillian Royse ◽  
...  
Keyword(s):  
Phospholipase C ◽  
Embryo Development ◽  
Specific Protein ◽  
Normal Embryo ◽  
Egg Activation ◽  
Sperm Factor ◽  
Mammalian Eggs ◽  
Mouse Eggs ◽  
Cytosolic Factor ◽  
Specific Trigger

Upon fertilisation by sperm, mammalian eggs are activated by a series of intracellular Ca2+ oscillations that are essential for embryo development. The mechanism by which sperm induces this complex signalling phenomenon is unknown. One proposal is that the sperm introduces an exclusive cytosolic factor into the egg that elicits serial Ca2+ release. The ‘sperm factor’ hypothesis has not been ratified because a sperm-specific protein that generates repetitive Ca2+ transients and egg activation has not been found. We identify a novel, sperm-specific phospholipase C, PLCζ, that triggers Ca2+ oscillations in mouse eggs indistinguishable from those at fertilisation. PLCζ removal from sperm extracts abolishes Ca2+ release in eggs. Moreover, the PLCζ content of a single sperm was sufficient to produce Ca2+ oscillations as well as normal embryo development to blastocyst. Our results are consistent with sperm PLCζ as the molecular trigger for development of a fertilised egg into an embryo.

scholarly journals The role of ATP in the differential ability of Sr2+ to trigger Ca2+ oscillations in mouse and human eggs

2021 ◽  
Author(s):  
Anna Storey ◽  
Khalil Elgmati ◽  
Yisu Wang ◽  
Paul Knaggs ◽  
Karl Swann
Keyword(s):  
Phospholipase C ◽  
Egg Activation ◽  
Apparent Difference ◽  
Free Medium ◽  
Inositol 1 ◽  
Atp Levels ◽  
Mature Mouse ◽  
Differential Ability ◽  
Mouse Eggs

Abstract At fertilization in mice and humans, the activation of the egg is caused by a series of repetitive Ca2+ oscillations which are initiated by phospholipase-C(zeta)ζ that generates inositol-1-4-5-trisphophate (InsP3). Ca2+ oscillations and egg activation can be triggered in mature mouse eggs by incubation in Sr2+ containing medium, but this does not appear to be effective in human eggs. Here we have investigated the reason for this apparent difference using mouse eggs, and human eggs that failed to fertilize after IVF or ICSI. Mouse eggs incubated in Ca2+-free, Sr2+-containing medium immediately underwent Ca2+ oscillations but human eggs consistently failed to undergo Ca2+ oscillations in the same Sr2+ medium. We tested the InsP3-receptor (IP3R) sensitivity directly by photo-release of caged InsP3 and found that mouse eggs were about 10 times more sensitive to InsP3 than human eggs. There were no major differences in the Ca2+ store content between mouse and human eggs. However, we found that the ATP concentration was consistently higher in mouse compared to human eggs. When ATP levels were lowered in mouse eggs by incubation in pyruvate-free medium, Sr2+ failed to cause Ca2+ oscillations. When pyruvate was added back to these eggs, the ATP levels increased and Ca2+ oscillations were induced. This suggests that ATP modulates the ability of Sr2+ to stimulate IP3R-induced Ca2+ release in eggs. We suggest that human eggs may be unresponsive to Sr2+ medium because they have a lower level of cytosolic ATP.

scholarly journals PLCζ or PAWP: revisiting the putative mammalian sperm factor that triggers egg activation and embryogenesis

2015 ◽  
Vol 21 (5) ◽  
pp. 383-388 ◽  
Author(s):  
Junaid Kashir ◽  
Michail Nomikos ◽  
Karl Swann ◽  
F. Anthony Lai
Keyword(s):  
Egg Activation ◽  
Mammalian Sperm ◽  
Sperm Factor

scholarly journals Characterization of a sperm factor for egg activation at fertilization of the newt Cynops pyrrhogaster

2007 ◽  
Vol 306 (2) ◽  
pp. 797-808 ◽  
Author(s):  
Yuichirou Harada ◽  
Tamami Matsumoto ◽  
Shino Hirahara ◽  
Akira Nakashima ◽  
Shuichi Ueno ◽  
...  
Keyword(s):  
Egg Activation ◽  
Cynops Pyrrhogaster ◽  
Sperm Factor

The sperm phospholipase C-ζ and Ca2+ signalling at fertilization in mammals

2016 ◽  
Vol 44 (1) ◽  
pp. 267-272 ◽  
Author(s):  
Karl Swann ◽  
F. Anthony Lai
Keyword(s):  
Phospholipase C ◽  
Embryo Development ◽  
Early Embryo ◽  
Egg Activation ◽  
Stable Form ◽  
Ph Domain ◽  
Vitro Fertilization ◽  
Sperm Factor ◽  
Internal Sources

A series of intracellular oscillations in the free cytosolic Ca2+ concentration is responsible for activating mammalian eggs at fertilization, thus initiating embryo development. It has been proposed that the sperm causes these Ca2+ oscillations after membrane fusion by delivering a soluble protein into the egg cytoplasm. We previously identified sperm-specific phospholipase C (PLC)-ζ as a protein that can trigger the same pattern of Ca2+ oscillations in eggs seen at fertilization. PLCζ appears to be the elusive sperm factor mediating egg activation in mammals. It has potential therapeutic use in infertility treatments to improve the rate of egg activation and early embryo development after intra-cytoplasmic sperm injection. A stable form of recombinant human PLCζ could be a prototype for use in such in vitro fertilization (IVF) treatments. We do not yet understand exactly how PLCζ causes inositol 1,4,5-trisphosphate (InsP3) production in eggs. Sperm PLCζ is distinct among mammalian PI-specific PLCs in that it is far more potent in triggering Ca2+ oscillations in eggs than other PLCs, but it lacks a PH domain that would otherwise be considered essential for binding to the phosphatidylinositol 4,5-bisphosphate (PIP2) substrate. PLCζ is also unusual in that it does not appear to interact with or hydrolyse plasma membrane PIP2. We consider how other regions of PLCζ may mediate its binding to PIP2 in eggs and how interaction of PLCζ with egg-specific factors could enable the hydrolysis of internal sources of PIP2.

scholarly journals Different triggers for calcium oscillations in mouse eggs involve a ryanodine-sensitive calcium store

1992 ◽  
Vol 287 (1) ◽  
pp. 79-84 ◽  
Author(s):  
K Swann
Keyword(s):  
G Protein ◽  
Calcium Oscillations ◽  
Release Mechanism ◽  
Protein Activity ◽  
Calcium Store ◽  
Thiol Reagent ◽  
Sperm Factor ◽  
Mouse Eggs

Relative intracellular free Ca2+ concentrations ([Ca2+]i) were monitored in mature unfertilized mouse eggs by measuring fluorescence of intracellular fluo3. A number of different agents were found to cause sustained repetitive transient [Ca2+]i oscillations. These were microinjection of a cytosolic sperm factor, sustained injection of Ins-(1,4,5)P1, or extracellular addition of the thiol reagent thimerosal. Stimulating G-protein activity by injection of guanosine 5′-[gamma-thio]triphosphate plus application of carbachol also caused [Ca2+]i oscillations, but less reliably than other stimuli. A role for Ca(2+)-induced Ca2+ release and a ryanodine-sensitive Ca2+ channel in mouse eggs was suggested by the finding that microinjection, or external addition, of ryanodine also caused [Ca2+]i increases. Furthermore, ryanodine, along with thimerosal, increased the sensitivity of eggs to Ca(2+)-induced [Ca2+]i oscillations. When ryanodine was added to eggs oscillating in response to the sperm factor, InsP3 or thimerosal, it caused a decrease in amplitude of oscillations and eventually a block of [Ca2+]i oscillations associated with a sustained elevation of [Ca2+]i. These data suggest that a ryanodine-sensitive Ca(2+)-release mechanism exists in mouse eggs and that a ryanodine-sensitive Ca2+ store plays a role in generating intracellular [Ca2+]i oscillations.

scholarly journals Potential role of a sperm-derived phospholipase C in triggering the egg-activating Ca2+ signal at fertilization

Reproduction ◽  
2001 ◽  
pp. 839-846 ◽  
Author(s):  
K Swann ◽  
J Parrington ◽  
KT Jones
Keyword(s):  
Membrane Fusion ◽  
Phospholipase C ◽  
Potential Role ◽  
Egg Activation ◽  
Gamete Fusion ◽  
Inositol 1,4,5 Trisphosphate ◽  
Sperm Factor

An increase in intracellular Ca2+ at fertilization is the trigger for egg activation in all species that have been studied. Exactly how sperm-egg interaction leads to this Ca2+ increase has not been established. There is increasing support for the hypothesis that the spermatozoon introduces a Ca2+-releasing protein into the egg cytoplasm after gamete membrane fusion. This review discusses the merits of this 'sperm factor' hypothesis and presents evidence indicating that the sperm factor, at least in mammals, consists of a phospholipase C with distinctive properties. This evidence leads us to propose that, after gamete fusion, a sperm-derived phospholipase C causes production of inositol 1,4,5- trisphosphate, which then generates Ca2+ waves from within the egg cytoplasm.

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