Egg Activation at Fertilization by a Soluble Sperm Protein

2016 ◽  
Vol 96 (1) ◽  
pp. 127-149 ◽  
Author(s):  
Karl Swann ◽  
F. Anthony Lai
Keyword(s):  
Mechanism Of Action ◽  
Empirical Studies ◽  
Specific Protein ◽  
Cellular Level ◽  
Egg Activation ◽  
Soluble Factor ◽  
Unresolved Issue ◽  
Sperm Protein ◽  
Mammalian Sperm ◽  
Intracellular Ca

The most fundamental unresolved issue of fertilization is to define how the sperm activates the egg to begin embryo development. Egg activation at fertilization in all species thus far examined is caused by some form of transient increase in the cytoplasmic free Ca2+ concentration. What has not been clear, however, is precisely how the sperm triggers the large changes in Ca2+ observed within the egg cytoplasm. Here, we review the studies indicating that the fertilizing sperm stimulates a cytosolic Ca2+ increase in the egg specifically by delivering a soluble factor that diffuses into the cytosolic space of the egg upon gamete membrane fusion. Evidence is primarily considered in species of eggs where the sperm has been shown to elicit a cytosolic Ca2+ increase by initiating Ca2+ release from intracellular Ca2+ stores. We suggest that our best understanding of these signaling events is in mammals, where the sperm triggers a prolonged series of intracellular Ca2+ oscillations. The strongest empirical studies to date suggest that mammalian sperm-triggered Ca2+ oscillations are caused by the introduction of a sperm-specific protein, called phospholipase C-zeta (PLCζ) that generates inositol trisphosphate within the egg. We will discuss the role and mechanism of action of PLCζ in detail at a molecular and cellular level. We will also consider some of the evidence that a soluble sperm protein might be involved in egg activation in nonmammalian species.

scholarly journals The cytosolic sperm factor that triggers Ca2+ oscillations and egg activation in mammals is a novel phospholipase C: PLCζ

Reproduction ◽  
2004 ◽  
Vol 127 (4) ◽  
pp. 431-439 ◽  
Author(s):  
K Swann ◽  
M G Larman ◽  
C M Saunders ◽  
F A Lai
Keyword(s):  
Membrane Fusion ◽  
Phospholipase C ◽  
Potential Role ◽  
Egg Activation ◽  
Specific Factor ◽  
Sperm Protein ◽  
Protein Factor ◽  
Inositol 1,4,5 Trisphosphate ◽  
Intracellular Ca ◽  
Sperm Factor

When sperm activate eggs at fertilization the signal for activation involves increases in the intracellular free Ca2+concentration. In mammals the Ca2+changes at fertilization consist of intracellular Ca2+oscillations that are driven by the generation of inositol 1,4,5-trisphosphate (InsP3). It is not established how sperm trigger the increases in InsP3and Ca2+at fertilization. One theory suggests that sperm initiate signals to activate the egg by introducing a specific factor into the egg cytoplasm after membrane fusion. This theory has been mainly based upon the observation that injecting a cytosolic sperm protein factor into eggs can trigger the same pattern of Ca2+oscillations induced by the sperm. We have recently shown that this soluble sperm factor protein is a novel form of phospholipase C (PLC), and it is referred to as PLCζ(zeta). We describe the evidence that led to the identification of PLCζ and discuss the issues relating to its potential role in fertilization.

Empirically Supported Psychological Treatments: EMDR

2012 ◽  
pp. 448-462
Author(s):  
C. Richard Spates ◽  
Sophie Rubin
Keyword(s):  
Mechanism Of Action ◽  
Stress Disorder ◽  
Empirical Studies ◽  
Future Research ◽  
Evidence Based ◽  
Psychological Treatments ◽  
Empirically Supported ◽  
Theoretical Mechanism ◽  
Effectiveness Trials ◽  
Empirical Foundation

In this chapter we review the empirical foundation for Eye Movement Desensitization and Reproessing Therapy (EMDR) for posttraumatic stress disorder. We present a brief description of the therapy, critically review recent primary and meta-analytic investigations concerning its efficacy and effectiveness, offer a summary of recent primary investigations that addressed the mechanism of action for EMDR, and based on this overall review, we suggest limitations with recommendations for future research. Recent empirical investigations of the efficacy of EMDR have improved along a number of important dimensions, and these along with the few completed effectiveness trials, position this therapy among evidence-based frontline interventions for PTSD. What is less thoroughly researched, and thus less well understood, are putative models of its theoretical mechanism of action. In addition to continuing specific improvements in research concerning efficacy and effectiveness, we recommend more and higher quality empirical studies of its mechanism of action.

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 The sperm protein SPACA4 is required for efficient fertilization in mice

2021 ◽  
Author(s):  
Sarah Herberg ◽  
Yoshitaka Fujihara ◽  
Andreas Blaha ◽  
Karin Panser ◽  
Kiyonari Kobayashi ◽  
...  
Keyword(s):  
Zona Pellucida ◽  
Knockout Mice ◽  
Mammalian Species ◽  
Wild Type ◽  
Sperm Protein ◽  
Mammalian Sperm ◽  
Fundamental Process ◽  
Mammalian Fertilization

Fertilization is the fundamental process that initiates the development of a new individual in all sexually reproducing species. Despite its importance, our understanding of the molecular players that govern mammalian sperm-egg interaction is incomplete, partly because many of the essential factors found in non-mammalian species do not have obvious mammalian homologs. We have recently identified the Ly6/uPAR protein Bouncer as a new, essential fertilization factor in zebrafish (Herberg et al., 2018). Here, we show that Bouncer's homolog in mammals, SPACA4, is also required for efficient fertilization in mice. In contrast to fish, where Bouncer is expressed specifically in the egg, SPACA4 is expressed exclusively in the testis. Male knockout mice are severely sub-fertile, and sperm lacking SPACA4 fail to fertilize wild-type eggs in vitro. Interestingly, removal of the zona pellucida rescues the fertilization defect of Spaca4-deficient sperm in vitro, indicating that SPACA4 is not required for the interaction of sperm and the oolemma but rather of sperm and zona pellucida. Our work identifies SPACA4 as an important sperm protein necessary for zona pellucida penetration during mammalian fertilization.

Stiffness is associated with hepatic stellate cell heterogeneity during liver fibrosis

2021 ◽  
Author(s):  
Enis Kostallari ◽  
Bo Wei ◽  
Delphine Sicard ◽  
Jiahui Li ◽  
Shawna A. Cooper ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Focal Adhesion ◽  
Hepatic Stellate Cell ◽  
Stellate Cell ◽  
Liver Stiffness ◽  
Specific Protein ◽  
Cellular Level ◽  
Fibrotic Liver ◽  
Soft Matrix

The fibrogenic wound-healing response in liver increases stiffness. Stiffness mechano-transduction in turn amplifies fibrogenesis. Here, we aimed to understand the distribution of stiffness in fibrotic liver, how it impacts hepatic stellate cell (HSC) heterogeneity and identify mechanisms by which stiffness amplifies fibrogenic responses. Magnetic resonance elastography and atomic force microscopy demonstrated a heterogenous distribution of liver stiffness at macroscopic and microscopic levels, respectively, in a carbon tetrachloride (CCl4) mouse model of liver fibrosis as compared to controls. High stiffness was mainly attributed to extracellular matrix dense areas. To identify a stiffness-sensitive HSC sub-population, we performed scRNA-seq on primary HSCs derived from healthy versus CCl4-treated mice. A sub-cluster of HSCs was matrix-associated with the most upregulated pathway in this sub-population being focal adhesion signaling, including a specific protein termed four and a half LIM domains protein 2 (FHL2). In vitro, FHL2 expression was increased in primary human HSCs cultured on stiff matrix as compared to HSCs on soft matrix. Moreover, FHL2 knockdown inhibited fibronectin and collagen 1 expression, whereas its overexpression promoted matrix production. In summary, we demonstrate stiffness heterogeneity at the whole organ, lobular, and cellular level which drives an amplification loop of fibrogenesis through specific focal adhesion molecular pathways.

399 SPERMATOZOA-MEDIATED GENE TRANSFER IS INFLUENCED BY SIZE, STRUCTURE, AND CONCENTRATION OF EXOGENOUS DNA

2007 ◽  
Vol 19 (1) ◽  
pp. 315
Author(s):  
W. B. Feitosa ◽  
M. P. Milazzotto ◽  
E. A. L. Martins ◽  
A. M. Rocha ◽  
J. L. Avanzo ◽  
...  
Keyword(s):  
Dna Sequences ◽  
Gel Electrophoresis ◽  
Sperm Cell ◽  
Reference Data ◽  
Size Structure ◽  
Specific Protein ◽  
Sperm Cells ◽  
Exogenous Dna ◽  
Mammalian Sperm ◽  
Cell Association

Mammalian sperm cells have a spontaneous ability to take up exogenous DNA in a process regulated by specific protein. However, little is known about the effect of exogenous DNA on sperm cell association. The aim of this work was to evaluate the effect of size, concentration, and structure of exogenous DNA sequence in apoptosis and oncosis induction and the association with spermatozoa. To evaluate the effect of size and concentration of exogenous DNA, sequences of 2.2, 5.5, and 8.5 kb were used at the concentrations of 500 ng (Experiment 1) or 5 × 1011 molecules (Experiment 2). To assess the effect of structure (Experiment 3), 3 sequences of approximately 500 bp were used, containing 65.7% of AT (AT sequence), 46.4% of AT (IN sequence), and 38.6% of AT (GC sequence). To evaluate apoptosis and oncosis in all treatments, sperm cells were incubated with exogenous DNA for 1 h, stained with 2 µL of Yo-Pro (100 µM) for 20 min, and 10 µL of propidium iodide (6 µM) for 10 min, and then analyzed by flow cytometry. To evaluate the transfection rates, sperm cells, after incubation, were separated from non-associated exogenous DNA by 2.5% gel electrophoresis. DNA (genomic and exogenous) was extracted and association rates obtained by real-time PCR. Data were submitted to ANOVA and compared by Tukey's test (P ≤ 0.05). The number of viable, apoptotic, oncosis, or in initial apoptosis/late oncosis spermatozoa incubated with different concentrations or sequences of exogenous DNA did not differ among groups. In Experiment 1, a higher DNA association with sperm cells was observed in the 5.5 kb sequence in comparison with the 2.2 and 8.5 kb. In Experiment 2, the 8.5 kb sequence had the lower association with the spermatozoa in comparison with the 2.2 kb and 5.5 kb. In Experiment 3, there was a higher interaction of the AT sequence when compared to IN and GC sequences. Reference data suggest that big sequences of exogenous DNA have advantages in the interaction with spermatozoa. The present work is the first one to show that the advantage of the big sequences on interaction became a disadvantage in relation to the ability of these cells to internalize this DNA. Table 1. Quantification of different exogenous DNA associated to sperm cells Financial support was provided by FAPESP 03/10234-7 and 03/07456-8.

scholarly journals Are Src family kinases involved in cell cycle resumption in rat eggs?

Reproduction ◽  
2004 ◽  
Vol 127 (4) ◽  
pp. 455-463 ◽  
Author(s):  
A Talmor-Cohen ◽  
R Tomashov-Matar ◽  
E Eliyahu ◽  
R Shapiro ◽  
R Shalgi
Keyword(s):  
Signal Transduction ◽  
Marine Invertebrate ◽  
Src Family Kinases ◽  
Egg Activation ◽  
Signal Transduction Pathways ◽  
Cortical Granules ◽  
Fusion Site ◽  
Intracellular Ca ◽  
Intensive Investigation ◽  
Mammalian Eggs

The earliest visible indications for the transition to embryos in mammalian eggs, known as egg activation, are cortical granules exocytosis (CGE) and resumption of meiosis (RM); these events are triggered by the fertilizing spermatozoon through a series of Ca2+transients. The pathways, within the egg, leading to the intracellular Ca2+release and to the downstream cellular events, are currently under intensive investigation. The involvement of Src family kinases (SFKs) in Ca2+release at fertilization is well supported in marine invertebrate eggs but not in mammalian eggs. In a previous study we have shown the expression and localization of Fyn, the first SFK member demonstrated in the mammalian egg. The purpose of the current study was to identify other common SFKs and resolve their function during activation of mammalian eggs. All three kinases examined: Fyn, c-Src and c-Yes are distributed throughout the egg cytoplasm. However, Fyn and c-Yes tend to concentrate at the egg cortex, though only Fyn is localized to the spindle as well. The different localizations of the various SFKs imply the possibility of their different functions within the egg. To examine whether SFKs participate in the signal transduction pathways during egg activation, we employed selective inhibitors of the SFKs activity ((PP2 and SU6656). The results demonstrate that RM, which is triggered by Ca2+elevation, is an SFK-dependent process, while CGE, triggered by either Ca2+elevation or protein kinase C (PKC), is not. The possible involvement of SFKs in the signal transduction pathways that lead from the sperm–egg fusion site downstream of the Ca2+release remains unclear.

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