The zinc spark is an inorganic signature of human egg activation

Duncan, Francesca E.; Que, Emily L.; Zhang, Nan; Feinberg, Eve C.; O’Halloran, Thomas V.; Woodruff, Teresa K.

doi:10.1038/srep24737

Cited by 100 publications

(97 citation statements)

References 40 publications

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“…Coordination of zinc to these ZP3 surface residues would provide a mechanism for forming protein-protein crosslinks within the ZP. We have observed zinc sparks in all of the mammalian species examined to date, 34, 35 suggesting that zinc-induced protein crosslinking could be an evolutionarily conserved mechanism for modulating ZP structure and function immediately after fertilization. Zinc-mediated crosslinks could also have roles later in preimplantation embryo development as the embryo travels along the oviduct, enters the mitotic phase, and prepares for implantation.…”

Section: Resultsmentioning

confidence: 90%

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Zinc sparks induce physiochemical changes in the egg zona pellucida that prevent polyspermy

et al. 2017

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During fertilization or chemically-induced egg activation, the mouse egg releases billions of zinc atoms in brief bursts known as ‘zinc sparks.’ The zona pellucida (ZP), a glycoprotein matrix surrounding the egg, is the first structure zinc ions encounter as they diffuse away from the plasma membrane. Following fertilization, the ZP undergoes changes described as ‘hardening’, which prevent multiple sperm from fertilizing the egg and thereby establish a block to polyspermy. A major event in zona hardening is cleavage of ZP2 proteins by ovastacin; however, the overall physiochemical changes contributing to zona hardening are not well understood. Using x-ray fluorescence microscopy, transmission and scanning electron microscopy, and biological function assays, we tested the hypothesis that zinc release contributes to ZP hardening. We found that the zinc content in the ZP increases by 300% following activation and that zinc exposure modulates the architecture of the ZP matrix. Importantly, zinc-induced structural changes of the ZP have a direct biological consequence; namely, they reduce the ability of sperm to bind to the ZP. These results provide a paradigm-shifting model in which fertilization-induced zinc sparks contribute to the polyspermy block by altering conformations of the ZP matrix. This adds a previously unrecognized factor, namely zinc, to the process of ZP hardening.

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Section: Resultsmentioning

confidence: 90%

“…and upon the species (mouse 34 ; non-human primate 34 ; human 35 ). Individual zinc sparks occur over a ca.…”

Section: Introductionmentioning

confidence: 99%

Zinc sparks induce physiochemical changes in the egg zona pellucida that prevent polyspermy

et al. 2017

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“…Zinc concentrations have been shown to fluctuate during various biological events, and have been identified as zinc sparks or zinc waves. 1,12 It is important to note that caspase-7 is more weakly apoptotic than caspase-3, and carries roles distinct from caspase-3. 56,57 Perhaps caspase-7 has a weakened affinity for zinc in order to carry out pivotal non-apoptotic roles constitutively.…”

Section: Discussionmentioning

confidence: 99%

Multiple Mechanisms of Zinc-Mediated Inhibition for the Apoptotic Caspases-3, -6, -7, and -8

et al. 2018

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Zinc is emerging as a widely used and important biological regulatory signal. Cellular zinc levels are tightly regulated by a complex array of zinc importer and exporters to control processes such as apoptotic cell death. While caspase inhibition by zinc has been reported previously, the reported inhibition constants were too weak to suggest a critical biological role for zinc-mediated inhibition. In this work we have adopted a method of assessing available zinc. This allowed assessment of the accurate inhibition constants for apoptotic caspases, caspase-3, -6, -7 and -8. Each of these caspases are inhibited by zinc at intracellular levels, however, with widely differing inhibition constants and different zinc binding stoichiometries. Caspase -3, -6 and -8 appear to be constitutively inhibited by typical zinc levels and this inhibition must be lifted to allow activation. The inhibition constant for caspase-7 (76 nM) is much weaker than for the other apoptotic caspases (2.6–6.9 nM) suggesting that caspase-7 is not inactivated by normal zinc concentrations but can be inhibited under conditions of zinc stress. Caspase-3, -7, and -8 were found to bind three, one, and two zincs respectively. In each of these caspases, zinc was present in the active site, in contrast to caspase-6, which binds one zinc allosterically. The most notable new mechanism to emerge from this work is for zinc-mediated inhibition of caspase-8. Zinc binds caspase-8 directly at the active site and at a second site. Zinc binding inhibits formation of the caspase-8 dimer, the activated form of the enzyme. Together these findings suggest that zinc plays a critical role in regulation of apoptosis by direct inactivation of caspases, in a manner that is unique for each caspase.

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“…There is a need to quantify extracellular biomarkers such as reactive oxygen species (ROS) , zinc (Zn 2+ ) and pH , in assisted reproductive technologies to allow for the assessment of cell health. This has applications in assisted reproduction for both human and agriculturally important species.…”

Section: Introductionmentioning

confidence: 99%

A biophotonic approach to measure pH in small volumes in vitro: Quantifiable differences in metabolic flux around the cumulus‐oocyte‐complex (COC)

McLennan

Saini

Sylvia

et al. 2019

Journal of Biophotonics

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Unfertilised eggs (oocytes) release chemical biomarkers into the medium surrounding them. This provides an opportunity to monitor cell health and development during assisted reproductive processes if detected in a non‐invasive manner. Here we report the measurement of pH using an optical fibre probe, OFP1, in 5 μL drops of culture medium containing single mouse cumulus oocyte complexes (COCs). This allowed for the detection of statistically significant differences in pH between COCs in culture medium with no additives and those incubated with either a chemical (cobalt chloride) or hormonal treatment (follicle stimulating hormone); both of which serve to induce the release of lactic acid into the medium immediately surrounding the COC. Importantly, OFP1 was shown to be cell‐safe with no inherent cell toxicity or light‐induced phototoxicity indicated by negative DNA damage staining. Pre‐measurement photobleaching of the probe reduced fluorescence signal variability, providing improved measurement precision (0.01‐0.05 pH units) compared to previous studies. This optical technology presents a promising platform for the measurement of pH and the detection of other extracellular biomarkers to assess cell health during assisted reproduction.

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The zinc spark is an inorganic signature of human egg activation

Cited by 100 publications

References 40 publications

Zinc sparks induce physiochemical changes in the egg zona pellucida that prevent polyspermy

Zinc sparks induce physiochemical changes in the egg zona pellucida that prevent polyspermy

Multiple Mechanisms of Zinc-Mediated Inhibition for the Apoptotic Caspases-3, -6, -7, and -8

A biophotonic approach to measure pH in small volumes in vitro: Quantifiable differences in metabolic flux around the cumulus‐oocyte‐complex (COC)

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