Oocyte activation: fundamental and clinical aspects

2020 ◽  
Vol 19 (5) ◽  
pp. 77-85
Author(s):  
Yu.Yu. Gromenko ◽  
◽  
E.F. Galimova ◽  
D.D. Gromenko ◽  
K.Sh. Galimov ◽  
...  

Fertilization and embryogenesis in mammals are initiated by a series of molecular events called ‘oocyte activation.’ This process includes a number of specific fluctuations of calcium ions in the cell with the involvement of specific phospholipase C ζ (PLCζ), an enzyme of spermatozoa introduced into the ooplasm during gamete fusion and recognized as the main factor responsible for inducing oocyte activation. Substantial biochemical and clinical evidence supports the role of PLCζ in this fundamental process, which is very important for the diagnosis and treatment of infertility. This literature review aims to provide some insight in the structure, mechanism of action, and regulation of PLCζ activity in healthy individuals and people with pathological conditions. Oocyte activation deficiency is associated with abnormalities in the structure, expression, and location of this enzyme in spermatozoa. Artificial activation of oocytes using ionophores, which is the only therapeutic option currently available for patients with its insufficiency, is being debated, especially in terms of its potential epigenetic effects on the embryo. Therefore, interest towards the development of human recombinant PLCζ as an alternative treatment is understandable. Researchers are currently discussing the possibility of diagnostic and clinical application of this enzyme to overcome male infertility associated with oocyte activation deficiency, as well as general aspects of this pathology. Key words: oocyte activation, infertility, calcium ions, phospholipase C ζ

2001 ◽  
Vol 280 (1) ◽  
pp. C100-C109 ◽  
Author(s):  
Orna Zagoory ◽  
Alex Braiman ◽  
Larisa Gheber ◽  
Zvi Priel

The goal of this work was to elucidate the molecular events underlying stimulation of ciliary beat frequency (CBF) induced by acetylcholine (ACh) in frog esophagus epithelium. ACh induces a profound increase in CBF and in intracellular Ca2+ concentration ([Ca2+]i) through M1 and M3 muscarinic receptors. The [Ca2+]i slowly decays to the basal level, while CBF stabilizes at an elevated level. These results suggest that ACh triggers Ca2+-correlated and -uncorrelated modes of ciliary stimulation. ACh response is abolished by the phospholipase C (PLC) inhibitor U-73122 and by depletion of intracellular Ca2+ stores but is unaffected by reduction of extracellular Ca2+ concentration and by blockers of Ca2+influx. Therefore, ACh activates PLC and mobilizes Ca2+solely from intracellular stores. The calmodulin inhibitors W-7 and calmidazolium attenuate the ACh-induced increase in [Ca2+]i but completely abolish the elevation in CBF. Therefore, elevation of [Ca2+]i is necessary for CBF enhancement but does not lead directly to it. The combined effect of Ca2+ elevation and of additional factors, presumably mobilized by Ca2+-calmodulin, results in a robust CBF enhancement.


1955 ◽  
Vol 32 (3) ◽  
pp. 451-467
Author(s):  
H. KACSER

The kinetics of the dark ground cortical change in fertilized sea urchins has been analysed. In normal eggs of Psammechinus miliaris the change appears to obey an autocatalytic mechanism. The evidence from artificial activation suggests that the initiation of the response is caused by a relatively unspecific event. The critical role of calcium is considered in relation to the evidence from eggs fertilized in capillary tubes. This suggests that calcium ions are not concerned with the initiation but with the propagation of the response. The primary change in activation may consist of an increase in permeability at the site of initiation.


Author(s):  
Usman Mir Khan ◽  
Ali Murad Khan ◽  
Umar Murad Khan ◽  
Zeliha Selamoğlu

Interest in goat farming is at its peak since the last decade of 20th century because the role of goat is well established in animal protein as well as in economic uplift of poor masses in the tropics and subtropics, but also constitutes an important component of traditional farming systems. Goat is a better option as farm animal in the tropics and subtropics as it can withstand dehydration and has better browsing habit which enables it to survive where cattle and sheep farming is difficult. Reproductive performance of does is of immense importance as contributing factor towards increased meat production and in finding out more prolific animals. This is the main factor affecting productivity of goats. Therefore, an improved reproduction rate will be an approach to increase in numbers. Reproductive seasonality represents a natural adaptation that provides important advantages for birth and offspring survival and development, as lambing/kidding coincides with good weather and maximum availability of forage. It is believed that photoperiod is the environmental factor other than food availability that determines the sexual activity in sheep and goat. This review paper focuses on the general aspects of seasonal factors influencing the goat’s reproductive efficiency.


Author(s):  
Kyungjun Uh ◽  
Alayna Hay ◽  
Paula Chen ◽  
Emily Reese ◽  
Kiho Lee

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.


Author(s):  
W.A. Jacob ◽  
R. Hertsens ◽  
A. Van Bogaert ◽  
M. De Smet

In the past most studies of the control of energy metabolism focus on the role of the phosphorylation potential ATP/ADP.Pi on the regulation of respiration. Studies using NMR techniques have demonstrated that the concentrations of these compounds for oxidation phosphorylation do not change appreciably throughout the cardiac cycle and during increases in cardiac work. Hence regulation of energy production by calcium ions, present in the mitochondrial matrix, has been the object of a number of recent studies.Three exclusively intramitochondnal dehydrogenases are key enzymes for the regulation of oxidative metabolism. They are activated by calcium ions in the low micromolar range. Since, however, earlier estimates of the intramitochondnal calcium, based on equilibrium thermodynamic considerations, were in the millimolar range, a physiological correlation was not evident. The introduction of calcium-sensitive probes fura-2 and indo-1 made monitoring of free calcium during changing energy metabolism possible. These studies were performed on isolated mitochondria and extrapolation to the in vivo situation is more or less speculative.


Acta Naturae ◽  
2016 ◽  
Vol 8 (2) ◽  
pp. 79-86 ◽  
Author(s):  
P. V. Elizar’ev ◽  
D. V. Lomaev ◽  
D. A. Chetverina ◽  
P. G. Georgiev ◽  
M. M. Erokhin

Maintenance of the individual patterns of gene expression in different cell types is required for the differentiation and development of multicellular organisms. Expression of many genes is controlled by Polycomb (PcG) and Trithorax (TrxG) group proteins that act through association with chromatin. PcG/TrxG are assembled on the DNA sequences termed PREs (Polycomb Response Elements), the activity of which can be modulated and switched from repression to activation. In this study, we analyzed the influence of transcriptional read-through on PRE activity switch mediated by the yeast activator GAL4. We show that a transcription terminator inserted between the promoter and PRE doesnt prevent switching of PRE activity from repression to activation. We demonstrate that, independently of PRE orientation, high levels of transcription fail to dislodge PcG/TrxG proteins from PRE in the absence of a terminator. Thus, transcription is not the main factor required for PRE activity switch.


Reproduction ◽  
2000 ◽  
pp. 57-68 ◽  
Author(s):  
J Garde ◽  
ER Roldan

Spermatozoa undergo exocytosis in response to agonists that induce Ca2+ influx and, in turn, activation of phosphoinositidase C, phospholipase C, phospholipase A2, and cAMP formation. Since the role of cAMP downstream of Ca2+ influx is unknown, this study investigated whether cAMP modulates phospholipase C or phospholipase A2 using a ram sperm model stimulated with A23187 and Ca2+. Exposure to dibutyryl-cAMP, phosphodiesterase inhibitors or forskolin resulted in enhancement of exocytosis. However, the effect was not due to stimulation of phospholipase C or phospholipase A2: in spermatozoa prelabelled with [3H]palmitic acid or [14C]arachidonic acid, these reagents did not enhance [3H]diacylglycerol formation or [14C]arachidonic acid release. Spermatozoa were treated with the phospholipase A2 inhibitor aristolochic acid, and dibutyryl-cAMP to test whether cAMP acts downstream of phospholipase A2. Under these conditions, exocytosis did not occur in response to A23187 and Ca2+. However, inclusion of dibutyryl-cAMP and the phospholipase A2 metabolite lysophosphatidylcholine did result in exocytosis (at an extent similar to that seen when cells were treated with A23187/Ca2+ and without the inhibitor). Inclusion of lysophosphatidylcholine alone, without dibutyryl-cAMP, enhanced exocytosis to a lesser extent, demonstrating that cAMP requires a phospholipase A2 metabolite to stimulate the final stages of exocytosis. These results indicate that cAMP may act downstream of phospholipase A2, exerting a regulatory role in the exocytosis triggered by physiological agonists.


2021 ◽  
pp. 193864002110097
Author(s):  
Suhas P. Dasari ◽  
Thomas M. Langer ◽  
Derek Parshall ◽  
Brian Law

Background: Large cystic osteochondral lesions of the talus (OLT) are challenging pathological conditions to treat, but particulated juvenile cartilage allografts (PJCAs) supplemented with bone grafts are a promising therapeutic option. The purpose of this project was to further elucidate the role of PJCA with concomitant bone autografts for treating large cystic OLTs with extensive subchondral bone involvement (greater than 150 mm2 in area and/or deeper than 5 mm). Methods: We identified 6 patients with a mean OLT area of 307.2 ± 252.4 mm2 and a mean lesion depth of 10.85 ± 6.10 mm who underwent DeNovo PJCA with bone autografting between 2013 and 2017. Postoperative outcomes were assessed with radiographs, Foot and Ankle Outcome Scores (FAOS), and visual pain scale scores. Results: At final follow-up (27.0 ± 12.59 weeks), all patients had symptomatic improvement and incorporation of the graft on radiographs. At an average of 62 ± 20.88 months postoperatively, no patients required a revision surgery. All patients contacted by phone in 2018 and 2020 reported they would do the procedure again in retrospect and reported an improvement in their symptoms relative to their preoperative state, especially with pain and in the FAOS activities of daily living subsection (91.93 ± 9.04 in 2018, 74.63 ± 26.86 in 2020). Conclusion: PJCA with concomitant bone autograft is a viable treatment option for patients with large cystic OLTs. Levels of Evidence: Level IV


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