Molecular triggers of egg activation at fertilization in mammals

Sanders, Jessica R.; Swann, Karl

doi:10.1530/rep-16-0123

Cited by 47 publications

(37 citation statements)

References 107 publications

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“…During this period the spindle microtubules are nonetheless highly dynamic [72,73], perpetually moving poleward and depolymerising at the poles in a motion dubbed poleward flux, which in oocytes is driven by kinesin-5 [72]. Fertilisation triggers a series of repetitive increases in intracellular free Ca 2+ concentration (Ca 2+ 'transients') [74] that drive destruction of Cyclin-B and Cytostatic Factor components and thereby trigger anaphase-II and the completion of meiosis [75]. In contrast to anaphase-I, the mechanism of anaphase-II has been described in detail in mouse.…”

Section: Spindle Function In Oocyte Meiosis-iimentioning

confidence: 99%

Segregating Chromosomes in the Mammalian Oocyte

Mihajlović

FitzHarris

2018

Current Biology

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Chromosome segregation errors in human oocytes lead to aneuploid embryos that cause infertility and birth defects. Here we provide an overview of the chromosome-segregation process in the mammalian oocyte, highlighting mechanistic differences between oocytes and somatic cells that render oocytes so prone to segregation error. These differences include the extremely large size of the oocyte cytoplasm, the unique geometry of meiosis-I chromosomes, idiosyncratic function of the spindle assembly checkpoint, and dramatically altered oocyte cell-cycle control and spindle assembly, as compared to typical somatic cells. We summarise recent work suggesting that aging leads to a further deterioration in fidelity of chromosome segregation by impacting multiple components of the chromosome-segregation machinery. In addition, we compare and contrast recent results from mouse and human oocytes, which exhibit overlapping defects to differing extents. We conclude that the striking propensity of the oocyte to mis-segregate chromosomes reflects the unique challenges faced by the spindle in a highly unusual cellular environment.

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Section: Spindle Function In Oocyte Meiosis-iimentioning

confidence: 99%

Segregating Chromosomes in the Mammalian Oocyte

Mihajlović

FitzHarris

2018

Current Biology

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“…But in insects, the trigger is independent of fertilization and is, instead, passage through the female reproductive tract (12)(13)(14)(15)(16). Both types of trigger cause a rise in Ca 2ϩ level in the oocyte cytoplasm, which is thought to set off the subsequent events by activating Ca 2ϩ / calmodulin-dependent kinase II (CaMKII) 1 and the phosphatase calcineurin (CN) (14,17). These enzymes are presumed to transduce the Ca 2ϩ signal downstream by phosphorylating or dephosphorylating maternally deposited proteins.…”

Section: Calcineurin-dependent Protein Phosphorylation Changes Duringmentioning

confidence: 99%

Calcineurin-dependent Protein Phosphorylation Changes During Egg Activation in Drosophila melanogaster

Zhang¹,

Ahmed-Braimah²,

Goldberg³

et al. 2019

Molecular & Cellular Proteomics

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Phosphoproteomic and global proteomic changes that occur during egg activation were quantified for the oocytes and eggs of Drosophila melanogaster with normal (control) or perturbed (CanB2 knockdown) calcineurin functions. We discovered broad influences of calcineurin on protein phosphorylation states in maturing oocytes and activating eggs. Our results illuminate the molecular mechanisms through which calcineurin regulates meiosis progression, protein translation, and signaling pathways during this critical developmental transition.

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“…In mammals, egg activation is triggered by sperm-induced Ca 2+ oscillations in the egg (Igusa and Miyazaki, 1986;Kline and Kline, 1992). A key role of these Ca 2+ oscillations is to downregulate, via a signalling pathway involving the Ca 2+ -dependent protein kinase gamma (CamKIIγ) and early mitotic inhibitor (Emi2), the maturation promotion factor (MPF) responsible for the metaphase II arrest of the egg (Sanders and Swann, 2016;Sobinoff et al, 2013). A later decline in mitogen-activated protein kinase (MAPK) activity correlates with the formation of pronuclei and entry into interphase of the first cell cycle.…”

Section: Introductionmentioning

confidence: 99%

PLCζ is the physiological trigger of the Ca2+ oscillations that induce embryogenesis in mammals but conception can occur in its absence

et al. 2017

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Activation of the egg by the sperm is the first, vital stage of embryogenesis. The sperm protein PLCζ has been proposed as the physiological agent that triggers the Ca oscillations that normally initiate embryogenesis. Consistent with this, recombinant PLCζ induces Ca oscillations in eggs and debilitating mutations in the gene are associated with infertility in men. However, there has been no evidence that knockout of the gene encoding PLCζ abolishes the ability of sperm to induce Ca oscillations in eggs. Here, we show that sperm derived from male mice fail to trigger Ca oscillations in eggs, cause polyspermy and thus demonstrate that PLCζ is the physiological trigger of these Ca oscillations. Remarkably, some eggs fertilized by PLCζ-null sperm can develop, albeit at greatly reduced efficiency, and after a significant time-delay. In addition, males are subfertile but not sterile, suggesting that in the absence of PLCζ, spontaneous egg activation can eventually occur via an alternative route. This is the first demonstration that fertilization without the normal physiological trigger of egg activation can result in offspring. PLCζ-null sperm now make it possible to resolve long-standing questions in fertilization biology, and to test the efficacy and safety of procedures used to treat human infertility.

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Molecular triggers of egg activation at fertilization in mammals

Abstract: trigger exocytosis via a mechanism that does not involve CAMKii. we discuss some recent developments in our understanding of these triggers for egg activation within the framework of cytosolic Ca 2+ signaling.Reproduction (2016) 152 R41-R50

Cited by 47 publications

References 107 publications

Segregating Chromosomes in the Mammalian Oocyte

Segregating Chromosomes in the Mammalian Oocyte

Calcineurin-dependent Protein Phosphorylation Changes During Egg Activation in Drosophila melanogaster

PLCζ is the physiological trigger of the Ca2+ oscillations that induce embryogenesis in mammals but conception can occur in its absence

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