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

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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Intracellular calcium oscillations and activation in horse oocytes injected with stallion sperm extracts or spermatozoa

Reproduction ◽

10.1530/rep.0.1260489 ◽

2003 ◽

pp. 489-499 ◽

Cited By ~ 20

Author(s):

SJ Bedford ◽

M Kurokawa ◽

K Hinrichs ◽

RA Fissore

Keyword(s):

Embryonic Development ◽

Intracellular Calcium ◽

Intracytoplasmic Sperm Injection ◽

Animal Species ◽

Mammalian Species ◽

Calcium Oscillations ◽

Large Animal ◽

Oocyte Activation ◽

Mouse Oocytes ◽

Species Specific

In oocytes from all mammalian species studied to date, fertilization by a spermatozoon induces intracellular calcium ([Ca(2+)](i)) oscillations that are crucial for appropriate oocyte activation and embryonic development. Such patterns are species-specific and have not yet been elucidated in horses; it is also not known whether equine oocytes respond with transient [Ca(2+)](i) oscillations when fertilized or treated with parthenogenetic agents. Therefore, the aims of this study were: (i) to characterize the activity of equine sperm extracts microinjected into mouse oocytes; (ii) to ascertain in horse oocytes the [Ca(2+)](i)-releasing activity and activating capacity of equine sperm extracts corresponding to the activity present in a single stallion spermatozoon; and (iii) to determine whether equine oocytes respond with [Ca(2+)](i) transients and activation when fertilized using the intracytoplasmic sperm injection (ICSI) procedure. The results of this study indicate that equine sperm extracts are able to induce [Ca(2+)](i) oscillations, activation and embryo development in mouse oocytes. Furthermore, in horse oocytes, injection of sperm extracts induced persistent [Ca(2+)](i) oscillations that lasted for >60 min and initiated oocyte activation. Nevertheless, injection of a single stallion spermatozoon did not consistently initiate [Ca(2+)](i) oscillations in horse oocytes. It is concluded that stallion sperm extracts can efficiently induce [Ca(2+)](i) responses and parthenogenesis in horse oocytes, and can be used to elucidate the signalling mechanism of fertilization in horses. Conversely, the inconsistent [Ca(2+)](i) responses obtained with sperm injection in horse oocytes may explain, at least in part, the low developmental success obtained using ICSI in large animal species.

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Design of novel oocyte activation methods: The role of zinc

Biology of Reproduction ◽

10.1093/biolre/ioab235 ◽

2021 ◽

Author(s):

Kyungjun Uh ◽

Alayna Hay ◽

Paula Chen ◽

Emily Reese ◽

Kiho Lee

Keyword(s):

Nuclear Transfer ◽

Meiotic Metaphase ◽

Oocyte Activation ◽

Metal Chelators ◽

Essential Step ◽

Mammalian Oocyte ◽

Cellular Events ◽

Artificial Oocyte Activation ◽

Artificial 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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Highly Specialized Ubiquitin-Like Modifications: Shedding Light into the UFM1 Enigma

Biomolecules ◽

10.3390/biom11020255 ◽

2021 ◽

Vol 11 (2) ◽

pp. 255

Author(s):

Katharina F. Witting ◽

Monique P.C. Mulder

Keyword(s):

Dna Repair ◽

Stress Response ◽

Embryonic Development ◽

Er Stress ◽

Unmet Needs ◽

Biological Function ◽

Post Translational Modification ◽

Er Stress Response ◽

Cellular Events ◽

Complex Signaling

Post-translational modification with Ubiquitin-like proteins represents a complex signaling language regulating virtually every cellular process. Among these post-translational modifiers is Ubiquitin-fold modifier (UFM1), which is covalently attached to its substrates through the orchestrated action of a dedicated enzymatic cascade. Originally identified to be involved embryonic development, its biological function remains enigmatic. Recent research reveals that UFM1 regulates a variety of cellular events ranging from DNA repair to autophagy and ER stress response implicating its involvement in a variety of diseases. Given the contribution of UFM1 to numerous pathologies, the enzymes of the UFM1 cascade represent attractive targets for pharmacological inhibition. Here we discuss the current understanding of this cryptic post-translational modification especially its contribution to disease as well as expand on the unmet needs of developing chemical and biochemical tools to dissect its role.

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Experimental manipulation of cerebral cortical areas in primates

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.1991.0019 ◽

1991 ◽

Vol 331 (1261) ◽

pp. 291-294 ◽

Cited By ~ 14

Keyword(s):

Molecular Mechanisms ◽

Experimental Manipulation ◽

Cognitive Capacity ◽

Brain Functions ◽

Cortical Areas ◽

Cellular Events ◽

Species Specific ◽

Higher Brain Functions ◽

Synaptic Circuitry ◽

Cytoarchitectonic Areas

The developmental mechanisms underlying the subdivision of the neocortex into structurally and functionally distinct areas is central to our understanding of the development of human cognitive capacity and the pathogenesis of congenital disorders of higher brain functions. The protomap hypothesis suggests how the cytoarchitectonic pattern of the cerebral cortex may be generated by a combination of intrinsic and extrinsic influences during embryonic development. Although little is known about the genetic and molecular mechanisms underlying this individual and species-specific diversity of cellular and synaptic architecture, experimental manipulation of development in the primate embryo provides a glimpse into the cascade of cellular events involved in the control of cell numbers, specification of neuronal phenotypes, their apportions into cytoarchitectonic areas, and establishment of area-specific synaptic circuitry.

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Regulation of the meiotic divisions of mammalian oocytes and eggs

Biochemical Society Transactions ◽

10.1042/bst20170493 ◽

2018 ◽

Vol 46 (4) ◽

pp. 797-806 ◽

Cited By ~ 10

Author(s):

Jessica R. Sanders ◽

Keith T. Jones

Keyword(s):

Cell Division ◽

Luteinizing Hormone ◽

Spindle Assembly Checkpoint ◽

Asymmetric Cell Division ◽

Homologous Chromosomes ◽

Mammalian Oocyte ◽

Cellular Events ◽

The Hours ◽

Meiosis I

Initiated by luteinizing hormone and finalized by the fertilizing sperm, the mammalian oocyte completes its two meiotic divisions. The first division occurs in the mature Graafian follicle during the hours preceding ovulation and culminates in an extreme asymmetric cell division and the segregation of the two pairs of homologous chromosomes. The newly created mature egg rearrests at metaphase of the second meiotic division prior to ovulation and only completes meiosis following a Ca2+ signal initiated by the sperm at gamete fusion. Here, we review the cellular events that govern the passage of the oocyte through meiosis I with a focus on the role of the spindle assembly checkpoint in regulating its timing. In meiosis II, we examine how the egg achieves its arrest and how the fertilization Ca2+ signal allows the initiation of embryo development.

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Ethanol Treatment Efficiently Induces Oocyte Activation and Further Embryonic Development in Rat.

Biology of Reproduction ◽

10.1093/biolreprod/78.s1.309 ◽

2008 ◽

Vol 78 (Suppl_1) ◽

pp. 309-309

Author(s):

Naomi Kashiwazaki ◽

Daisuke Sano ◽

Yuki Yamamoto ◽

Tomo Samejima ◽

Junya Ito

Keyword(s):

Embryonic Development ◽

Oocyte Activation ◽

Ethanol Treatment

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Prematurational Culture with 3-Isobutyl-1-methylxanthine Synchronizes Meiotic Progression of the Germinal Vesicle Stage and Improves Nuclear Maturation and Embryonic Development in In Vitro-grown Bovine Oocytes

Journal of Reproduction and Development ◽

10.1262/jrd.2013-082 ◽

2014 ◽

Vol 60 (1) ◽

pp. 9-13 ◽

Cited By ~ 6

Author(s):

Weiping HUANG ◽

Masashi NAGANO ◽

Sung-Sik KANG ◽

Yojiro YANAGAWA ◽

Yoshiyuki TAKAHASHI

Keyword(s):

Embryonic Development ◽

Germinal Vesicle ◽

Nuclear Maturation ◽

Meiotic Progression ◽

Bovine Oocytes

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Ades: New Ecological Families of Species-Specific Frequency Distributions that Describe Repeated Spatial Samples with an Intrinsic Power-Law Variance-Mean Property

Journal of Animal Ecology ◽

10.2307/4388 ◽

1985 ◽

Vol 54 (3) ◽

pp. 931 ◽

Cited By ~ 39

Author(s):

J. N. Perry ◽

L. R. Taylor

Keyword(s):

Power Law ◽

Frequency Distributions ◽

Specific Frequency ◽

Species Specific

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Microinjection of mouse phospholipase Cζ complementary RNA into mare oocytes induces long-lasting intracellular calcium oscillations and embryonic development

Reproduction Fertility and Development ◽

10.1071/rd08115 ◽

2008 ◽

Vol 20 (8) ◽

pp. 875 ◽

Cited By ~ 21

Author(s):

Sylvia J. Bedford-Guaus ◽

Sook-Young Yoon ◽

Rafael A. Fissore ◽

Young-Ho Choi ◽

Katrin Hinrichs

Keyword(s):

Embryonic Development ◽

Nuclear Transfer ◽

Calcium Oscillations ◽

Oocyte Activation ◽

Parthenogenetic Activation ◽

Assisted Reproduction Technologies ◽

Significant Difference ◽

Developmental Rates ◽

Advanced Stages ◽

Consistent Method

Methods presently used to activate mare oocytes for assisted reproduction technologies provide low rates of advanced embryonic development. Because phospholipase Cζ (PLCζ) is the postulated sperm-borne factor responsible for oocyte activation at fertilisation, the aim of the present study was to investigate the pattern of [Ca2+]i oscillations and developmental rates achieved by microinjection of three concentrations of mouse PLCζ complementary (c) RNA (1, 0.5 or 0.25 μg μL–1) into mare oocytes. The frequency of [Ca2+]i oscillations was no different (P > 0.05) after injection of 1, 0.5 or 0.25 μg μL–1 PLCζ cRNA (41.1 ± 5.3, 47 ± 4.0 and 55.4 ± 9.0, respectively). However, [Ca2+]i oscillations persisted longest (P < 0.05) for oocytes injected with 0.5 μg μL–1 PLCζ cRNA (570.7 ± 64.2 min). There was no significant difference in cleavage rates after injection of the three concentrations of PLCζ (P > 0.05; range 97–100%), but the proportion of oocytes reaching advanced stages of embryonic development (>64 nuclei) was significantly lower for oocytes injected with 0.25 μg μL–1 PLCζ cRNA (3%) than for those injected with 1 μg μL–1 PLCζ cRNA (15%). Based on these results, microinjection of PLCζ may prove an effective and consistent method for the parthenogenetic activation of mare oocytes for nuclear transfer and provides a physiologically relevant tool with which to study fertilisation-dependent [Ca2+]i signalling in this species.

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