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Kevin Coward - One of the best experts on this subject based on the ideXlab platform.
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Oocyte Activation Deficiency and Advances to Overcome
In Vitro Fertilization, 2019Co-Authors: Marc Yeste, Celine Jones, Siti Nornadhirah Amdani, Kevin CowardAbstract:This chapter defines Oocyte Activation and the main molecular events related to this crucial phenomenon which takes place upon sperm-Oocyte fusion. Oocytes are arrested at metaphase-II until fertilization and are alleviated from arrest by their interaction with a sperm-borne Oocyte Activation factor (SOAF). This factor triggers a series of calcium (Ca2+) oscillations which release the Oocyte from metaphase-II and initiates the first sequence of embryogenesis. While different theories and protein candidates have been proposed to explain the mechanism by which the SOAF acts, mounting evidence indicates that a sperm-soluble factor, phospholipase C zeta (PLCζ), is the protein which evokes Ca2+ oscillations in the ooplasm. Here, we review the cascade of downstream events triggered by PLCζ and refer to the vital role of Ca2+ homeostasis during Oocyte Activation. Failure of the Oocyte to activate is known to underlie certain types of human infertility, but the diagnosis of this condition is complex, and treatment options are limited at present to the use of artificial Oocyte activators, which operate via electrical, mechanical and chemical means. As chemical Oocyte activators are the most commonly used at present, we briefly review the available clinical data for these agents, both in terms of their efficiency and safety, and discuss how alternative, more endogenous, methods could alleviate growing global concerns surrounding the use of artificial Oocyte activating agents.
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Oocyte Activation and Fertilisation: Crucial Contributors from the Sperm and Oocyte
Results and problems in cell differentiation, 2017Co-Authors: Marc Yeste, Celine Jones, Siti Nornadhirah Amdani, Kevin CowardAbstract:This chapter intends to summarise the importance of sperm- and Oocyte-derived factors in the processes of sperm-Oocyte binding and Oocyte Activation. First, we describe the initial interaction between sperm and the zona pellucida, with particular regard to acrosome exocytosis. We then describe how sperm and Oocyte membranes fuse, with special reference to the discovery of the sperm protein IZUMO1 and its interaction with the Oocyte membrane receptor JUNO. We then focus specifically upon Oocyte Activation, the fundamental process by which the Oocyte is alleviated from metaphase II arrest by a sperm-soluble factor. The identity of this sperm factor has been the source of much debate recently, although mounting evidence, from several different laboratories, provides strong support for phospholipase C ζ (PLCζ), a sperm-specific phospholipase. Herein, we discuss the evidence in support of PLCζ and evaluate the potential role of other candidate proteins, such as post-acrosomal WW-binding domain protein (PAWP/WBP2NL). Since the cascade of downstream events triggered by the sperm-borne Oocyte Activation factor heavily relies upon specialised cellular machinery within the Oocyte, we also discuss the critical role of Oocyte-borne factors, such as the inositol trisphosphate receptor (IP3R), protein kinase C (PKC), store-operated calcium entry (SOCE) and calcium/calmodulin-dependent protein kinase II (CaMKII), during the process of Oocyte Activation. In order to place the implications of these various factors and processes into a clinical context, we proceed to describe their potential association with Oocyte Activation failure and discuss how clinical techniques such as the in vitro maturation of Oocytes may affect Oocyte Activation ability. Finally, we contemplate the role of artificial Oocyte activating agents in the clinical rescue of Oocyte Activation deficiency and discuss options for more endogenous alternatives.
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Oocyte Activation deficiency: a role for an Oocyte contribution?
Human reproduction update, 2015Co-Authors: Marc Yeste, Celine Jones, Siti Nornadhirah Amdani, S Patel, Kevin CowardAbstract:Infertility affects between 10 and 16% of couples worldwide. Twenty to 30% of cases of infertility are due to a male factor, 20-35% to a female factor, and 25-40% are due to both male and female factors. In ∼10-25% of cases, the precise underlying cause remains unclear. IVF or ICSI followed by embryo transfer can be very appropriate treatment options in cases of female tubal damage, ovulatory failure or male-factor infertility. While the use of IVF has been reported to be suitable for many infertile couples, normal IVF cycles can fail in some cases. While ICSI can represent a powerful alternative in cases of IVF failure, complete fertilization failure can still occur in 1-5% of ICSI cycles. This can be due to a variety of factors and while commonly attributed to deficiency of sperm factors, it is very likely that abnormalities in crucial Oocyte factors could also play a key role.A critical literature review using PubMed was performed between April 2014 and July 2015 targeting studies concerning sperm and Oocyte factors that could account for Oocyte Activation deficiency, and including studies of in vitro Oocyte maturation in human Oocytes, and animal models.Accumulating evidence indicates that phospholipase C zeta (PLCζ) is the sperm Oocyte Activation factor, although recent studies claim that another sperm protein known as post-acrosomal WWP-binding domain protein could also play a significant role in the Activation of Oocytes. The present review discusses our current understanding of these two proteins but emphasizes that defects in the molecular machinery within the Oocyte that interacts with such sperm proteins may also represent an underlying cause of fertilization failure and infertility, especially in cases where there is no obvious indication for sperm deficiency. Abnormalities in such mechanisms are highly likely to exert influence over the pulsatile release of calcium within the ooplasm, the critical signal that controls Oocyte Activation events. These molecular targets within the Oocyte are rarely, if ever, considered clinically. We therefore recommend that future diagnostic assays should be developed to consider the inositol triphosphate receptor, protein kinase C, proteins associated with stored operated calcium entry calcium/calmodulin-dependent protein kinase II and mitogen-activated protein kinase. Development of such assays would represent a significant step forward in the diagnosis of Oocyte Activation deficiency and may identify a series of potential therapeutic targets.The present review provides a general overview of how a combination of sperm and Oocyte factors can underlie Oocyte Activation deficiency, but pays particular attention to the less appreciated role of the Oocyte. Enhanced research within this realm is much warranted and may establish new approaches for the diagnosis and treatment of infertility.
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Sperm Factors and Oocyte Activation: Current Controversies and Considerations
Biology of reproduction, 2015Co-Authors: Siti Nornadhirah Amdani, Celine Jones, Marc Yeste, Kevin CowardAbstract:The beginning of embryogenesis is preceded by a sequence of events mediated by the release of intracellular calcium in the ooplasm, a multifaceted process known as Oocyte Activation. It is now well established that a sperm protein factor introduced into the Oocyte at the time of gamete fusion is responsible for initiating the cascade of signaling events involved. Several sperm proteins have been hypothesized as the sperm Oocyte-activating factor (SOAF) over the years, with phospholipase C zeta 1 (PLCZ1 or PLCzeta) emerging as the strongest candidate. A large body of consistent and reproducible evidence, from both biochemical and clinical settings, has accumulated in support of PLCzeta, and data clearly demonstrate that Oocyte Activation ability can be rescued in PLCzeta-deficient sperm by either PLCzeta cRNA or recombinant PLCzeta protein. However, a series of recent publications has challenged the dominance of PLCzeta and proposed an alternative candidate protein, WBP2 N-terminal like (WBP2NL or PAWP). These events have led to significant debate, fueled by the opposing views of two independent laboratories, each defending its own respective SOAF candidate. This raises important questions with regards to the relative importance of these two proteins in diagnostic and therapeutic medicine, and invites urgent research attention. Here, it is our intention to reflect upon this now very controversial area in order to engage the scientific and clinical communities in addressing the true importance of these two sperm proteins.
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Oocyte Activation and Phospholipase C Zeta (PLCζ): Male Infertility and Implications for Therapeutic Intervention
Phospholipases in Health and Disease, 2014Co-Authors: Junaid Kashir, Celine Jones, Kevin CowardAbstract:Infertility is a condition that now affects an estimated one in seven couples. In approximately 40 % of cases, the primary cause of infertility rests with male-derived factors associated with a variety of anatomical, physiological, and molecular deficiencies. In a proportion of such cases, the functional ability of sperm to successfully fertilise and activate the Oocyte is compromised. While assisted reproductive technology can successfully circumvent some of these issues via the application of artificial Oocyte-activating agents, there is significant ongoing debate as to whether these chemical agents should be replaced with an endogenous alternative. Phospholipase C zeta (PLCζ) is the sperm-specific protein responsible for activating the quiescent Oocyte following gamete fusion. Identified in a number of mammalian and non-mammalian organisms, PLCζ plays a fundamental role in the process of Oocyte Activation by inducing the controlled release of calcium in the ooplasm via an inositol triphosphate (IP3)-mediated signalling cascade. A growing body of evidence shows clear association between abnormalities in PLCζ structure, expression, localisation, and function to characterised states of human male infertility. Consequently there is significant global interest in PLCζ as both an endogenous therapeutic target to rescue infertile states associated with PLCζ-linked Oocyte Activation deficiency, and a diagnostic marker for Oocyte Activation ability. Here, we discuss the present status of PLCζ research and contemplate future applications of this fundamental sperm PLC in the clinic.
Akira Sato - One of the best experts on this subject based on the ideXlab platform.
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The Oocyte Activation and Ca2+ oscillation-inducing abilities of mouse and human dead (sonicated) spermatozoa.
Zygote (Cambridge England), 2009Co-Authors: Hiroyuki Yazawa, Kaoru Yanagida, Shoutaro Hayashi, Akira SatoAbstract:In ICSI procedures, it is well known that the selection of viable (live) spermatozoa and certain types of immobilization prior to injection is very important for obtaining successful results, but unfortunately there are rare situations when only immotile spermatozoa are available (such as in severe asthenozoospermia or necrozoospermia). In such cases, failure of Oocyte Activation after ICSI often occurs and may be due to the lack of SOAF (sperm-borne Oocyte activating factor) activity. In order to investigate the SOAF activities of dead spermatozoa, mouse and human spermatozoa were immobilized (killed by sonication), maintained in THF medium for varying time intervals (up to 72 h) and then injected into mature unfertilized mouse Oocytes. Injected mouse Oocytes were examined for their Activation, development into blastocysts and Ca 2+ responses by imaging and confocal laser scanning microscope. The rates of Oocyte Activation, blastocyst development and normal patterns of Ca 2+ oscillation from the killed-sperm-injected Oocytes decreased gradually in accordance with the maintenance interval between sonication and injection. For injection with mouse sonicated spermatozoa, the rate of normal Ca 2+ oscillations declined first (after a 3 h maintenance interval) and then blastocyst development was gradually obstructed (after approx. 10 h). The Oocyte Activation-inducing ability of dead spermatozoa was maintained for a relatively long period, but began to decline after 20 h. The Activation rates and Ca 2+ response of the Oocytes that were injected with human sonicated spermatozoa decreased earlier than those injected with mouse spermatozoa. Although the Oocyte Activation-inducing ability was maintained for a relatively long time after the death of the spermatozoa, embryo development into blastocysts and the rate of normal Ca 2+ oscillations declined after a short maintenance interval between sonication and injection. The Ca 2+ response seemed to be the most sensitive indicator for the evaluating the SOAF activity of dead (killed) spermatozoa.
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Human round spermatids from azoospermic men exhibit Oocyte-Activation and Ca2+ oscillation-inducing activities.
Zygote (Cambridge England), 2007Co-Authors: H. Yazawa, Kaoru Yanagida, Akira SatoAbstract:During mammalian fertilization, intracellular Ca 2+ oscillations are important for both Oocyte Activation and embryonic development. As the ability of round spermatids (ROS) to induce Ca 2+ oscillations and Oocyte Activation is different between species, we examined Ca 2+ oscillation- and Oocyte Activation-inducing abilities of human ROS originating from patients with non-obstructive azoospermia. Human ROS from 11 non-obstructive azoospermic patients were collected during their TESE–ICSI cycles. Following injection into mature unfertilized mouse Oocytes, we examined the Oocyte-activating and Ca 2+ oscillation-inducing activities of ROS by using Ca 2+ imaging and confocal laser scanning microscopy (mouse test). In these 11 cases, clinical TESE–ICSI using mature testicular spermatozoa was successful, with the exception of one case in which only one sperm-injected Oocyte was not fertilized. The mean fertilization rate was 70.1% (40–100%); the mean cleavage rate was 97.9% (46/47). Two pregnancies were established from 10 transfer cycles (PR; 20%). When the ROS from these patients were injected into mouse Oocytes, the ROS from all patients induced at least some intracellular Ca 2+ oscillations (25–100%). In all patients, 40 out of 82 Oocytes injected with ROS exhibited normal oscillation patterns of [Ca 2+ ]i. Human spermatogenetic cells acquired Oocyte-activating and Ca 2+ oscillation-inducing abilities at the round spermatid stage, an earlier stage than found for rodent cells. These data indicate that human ROS might be useful for clinical treatments of non-obstructive azoospermic patients exhibiting mature spermatozoa in biopsied specimens.
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Successful pregnancy after ICSI with strontium Oocyte Activation in low rates of fertilization.
Reproductive biomedicine online, 2006Co-Authors: Kaoru Yanagida, Haruo Katayose, Syotaro Hayashi, Kazuto Morozumi, Akira SatoAbstract:Fertilization failure (complete fertilization failure or low fertilization rates) after intracytoplasmic sperm injection (ICSI) can occur in rare cases. In the majority of these cases, the unfertilized Oocytes are inactivated. Assisted Oocyte Activation was applied as a treatment option for a case of low fertilization rate as a clinical trial. A patient with a low fertilization rate (ranging from 0% to 33.3%; mean = 17.0%) after eight previous ICSI cycles at another hospital, was diagnosed with fertilization failure. The most likely cause of fertilization failure was failure of Oocyte Activation. Therefore, artificial Oocyte Activation by strontium treatment was combined with ICSI to achieve viable fertilized Oocytes. Oocytes were stimulated with strontium (10 mM SrCl(2), 60 min) approximately 30 min after ICSl. Six injected Oocytes were stimulated and all were then successfully fertilized. Two blastocysts were transferred into the uterus, resulting in a pregnancy and birth. A second pregnancy was achieved following implantation of two cryopreserved embryos (one blastocyst and one morula). In conclusion, strontium treatment was found to be an effective method for artificial Oocyte Activation in a case with a low fertilization rate after ICSI.
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Oocyte Activation and Ca2+ oscillation-inducing abilities of mouse round/elongated spermatids and the developmental capacities of embryos from spermatid injection
Human reproduction (Oxford England), 2001Co-Authors: Hiroyuki Yazawa, Kaoru Yanagida, Akira SatoAbstract:To investigate differences in fertilization mechanisms and the potential clinical use of round/elongated spermatid, we conducted detailed studies of Oocyte Activation and Ca 2+ oscillation-inducing abilities in these immature sperm cells and compared these abilities against those of mature spermatozoa. When round spermatids from B 6 D 2 F 1 mice were injected, none of the Oocytes was activated and no intracellular Ca 2+ ([Ca 2+ ] i ) increases were observed. Elongated spermatids could induce Activation normally in 87% of injected Oocytes, but Ca 2+ oscillation could not be induced at all and most of the Oocytes (94%) exhibited only several transient [Ca 2+ ] i rises (transient patterns). Because normal offspring could be obtained when embryos through elongated spermatid injection were transferred to foster mothers, it seems that a normal oscillation pattern of [Ca 2+ ] i is not essential for normal fertilization and embryo development. [Ca 2+ ] i patterns of injected Oocytes changed from transient patterns to oscillation patterns while the injected immature sperm cells were maturing to spermatozoa. Dissociations were seen between the timing of appearance of Oocyte Activation and that of Ca 2+ oscillation-inducing abilities in maturing sperm cells. These dissociations may be due to differences in the thresholds to Oocyte Activation and Ca 2+ oscillation-inducing factor for inducing Oocyte Activation and Ca 2+ oscillation.
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Oocyte Activation induced by spermatids and the spermatozoa.
International Journal of Andrology, 2000Co-Authors: Kaoru Yanagida, Hiroyuki Yazawa, Haruo Katayose, Yasuyuki Kimura, Syotaro Hayashi, Akira SatoAbstract:It has been reported that a sperm factor (SF) found in spermatozoa plays a critical role in fertilization. However, particulars of the Oocyte-activating and Ca2+ oscillation (Ca-Os)-inducing abilities of this SF remain unknown. We examined these abilities of spermatids in mouse, hamster and human by a mouse test (injection of spermatids into mouse Oocytes). In mice, the round spermatids (ROS), elongated spermatids (ELS) and spermatozoa activated 0%, 93% and 92% of the Oocytes, respectively. ROS injection resulted in no Ca-Os (type C). ELS induced a normal oscillation (type A) at 0% and an abnormal oscillation (type B) at 94%. Mouse spermatozoa induced type A Ca-Os at 90%. For mice, Oocyte-activating and Ca2+ oscillation-inducing ability arose in different phases of spermiogenesis. We also observed this differential timing for hamster spermatids. Hamster ROS activated 74% of Oocyte (ELS: 90%, sperm: 86%). Human ROS activated 64% of Oocytes (sperm: 100%), but only 35% of the Oocytes showed type A Ca-Os. These results indicate that Oocyte Activation generally occurs between the ROS and ELS phases, although these phases differ among species. They also indicate that Oocyte Activation is not necessarily accompanied by Ca-Os. These findings suggest the existence of different thresholds at which the SF induces Oocyte Activation and Ca2+ oscillation, or of different factors that induce Oocyte Activation and Ca-Os. We found SF to be clinically impaired in 0.9% of ICSI patients. A combination of artificial Oocyte Activation and ICSI proved effective with such patients.
Celine Jones - One of the best experts on this subject based on the ideXlab platform.
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Oocyte Activation Deficiency and Advances to Overcome
In Vitro Fertilization, 2019Co-Authors: Marc Yeste, Celine Jones, Siti Nornadhirah Amdani, Kevin CowardAbstract:This chapter defines Oocyte Activation and the main molecular events related to this crucial phenomenon which takes place upon sperm-Oocyte fusion. Oocytes are arrested at metaphase-II until fertilization and are alleviated from arrest by their interaction with a sperm-borne Oocyte Activation factor (SOAF). This factor triggers a series of calcium (Ca2+) oscillations which release the Oocyte from metaphase-II and initiates the first sequence of embryogenesis. While different theories and protein candidates have been proposed to explain the mechanism by which the SOAF acts, mounting evidence indicates that a sperm-soluble factor, phospholipase C zeta (PLCζ), is the protein which evokes Ca2+ oscillations in the ooplasm. Here, we review the cascade of downstream events triggered by PLCζ and refer to the vital role of Ca2+ homeostasis during Oocyte Activation. Failure of the Oocyte to activate is known to underlie certain types of human infertility, but the diagnosis of this condition is complex, and treatment options are limited at present to the use of artificial Oocyte activators, which operate via electrical, mechanical and chemical means. As chemical Oocyte activators are the most commonly used at present, we briefly review the available clinical data for these agents, both in terms of their efficiency and safety, and discuss how alternative, more endogenous, methods could alleviate growing global concerns surrounding the use of artificial Oocyte activating agents.
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Oocyte Activation and Fertilisation: Crucial Contributors from the Sperm and Oocyte
Results and problems in cell differentiation, 2017Co-Authors: Marc Yeste, Celine Jones, Siti Nornadhirah Amdani, Kevin CowardAbstract:This chapter intends to summarise the importance of sperm- and Oocyte-derived factors in the processes of sperm-Oocyte binding and Oocyte Activation. First, we describe the initial interaction between sperm and the zona pellucida, with particular regard to acrosome exocytosis. We then describe how sperm and Oocyte membranes fuse, with special reference to the discovery of the sperm protein IZUMO1 and its interaction with the Oocyte membrane receptor JUNO. We then focus specifically upon Oocyte Activation, the fundamental process by which the Oocyte is alleviated from metaphase II arrest by a sperm-soluble factor. The identity of this sperm factor has been the source of much debate recently, although mounting evidence, from several different laboratories, provides strong support for phospholipase C ζ (PLCζ), a sperm-specific phospholipase. Herein, we discuss the evidence in support of PLCζ and evaluate the potential role of other candidate proteins, such as post-acrosomal WW-binding domain protein (PAWP/WBP2NL). Since the cascade of downstream events triggered by the sperm-borne Oocyte Activation factor heavily relies upon specialised cellular machinery within the Oocyte, we also discuss the critical role of Oocyte-borne factors, such as the inositol trisphosphate receptor (IP3R), protein kinase C (PKC), store-operated calcium entry (SOCE) and calcium/calmodulin-dependent protein kinase II (CaMKII), during the process of Oocyte Activation. In order to place the implications of these various factors and processes into a clinical context, we proceed to describe their potential association with Oocyte Activation failure and discuss how clinical techniques such as the in vitro maturation of Oocytes may affect Oocyte Activation ability. Finally, we contemplate the role of artificial Oocyte activating agents in the clinical rescue of Oocyte Activation deficiency and discuss options for more endogenous alternatives.
-
Oocyte Activation deficiency: a role for an Oocyte contribution?
Human reproduction update, 2015Co-Authors: Marc Yeste, Celine Jones, Siti Nornadhirah Amdani, S Patel, Kevin CowardAbstract:Infertility affects between 10 and 16% of couples worldwide. Twenty to 30% of cases of infertility are due to a male factor, 20-35% to a female factor, and 25-40% are due to both male and female factors. In ∼10-25% of cases, the precise underlying cause remains unclear. IVF or ICSI followed by embryo transfer can be very appropriate treatment options in cases of female tubal damage, ovulatory failure or male-factor infertility. While the use of IVF has been reported to be suitable for many infertile couples, normal IVF cycles can fail in some cases. While ICSI can represent a powerful alternative in cases of IVF failure, complete fertilization failure can still occur in 1-5% of ICSI cycles. This can be due to a variety of factors and while commonly attributed to deficiency of sperm factors, it is very likely that abnormalities in crucial Oocyte factors could also play a key role.A critical literature review using PubMed was performed between April 2014 and July 2015 targeting studies concerning sperm and Oocyte factors that could account for Oocyte Activation deficiency, and including studies of in vitro Oocyte maturation in human Oocytes, and animal models.Accumulating evidence indicates that phospholipase C zeta (PLCζ) is the sperm Oocyte Activation factor, although recent studies claim that another sperm protein known as post-acrosomal WWP-binding domain protein could also play a significant role in the Activation of Oocytes. The present review discusses our current understanding of these two proteins but emphasizes that defects in the molecular machinery within the Oocyte that interacts with such sperm proteins may also represent an underlying cause of fertilization failure and infertility, especially in cases where there is no obvious indication for sperm deficiency. Abnormalities in such mechanisms are highly likely to exert influence over the pulsatile release of calcium within the ooplasm, the critical signal that controls Oocyte Activation events. These molecular targets within the Oocyte are rarely, if ever, considered clinically. We therefore recommend that future diagnostic assays should be developed to consider the inositol triphosphate receptor, protein kinase C, proteins associated with stored operated calcium entry calcium/calmodulin-dependent protein kinase II and mitogen-activated protein kinase. Development of such assays would represent a significant step forward in the diagnosis of Oocyte Activation deficiency and may identify a series of potential therapeutic targets.The present review provides a general overview of how a combination of sperm and Oocyte factors can underlie Oocyte Activation deficiency, but pays particular attention to the less appreciated role of the Oocyte. Enhanced research within this realm is much warranted and may establish new approaches for the diagnosis and treatment of infertility.
-
Sperm Factors and Oocyte Activation: Current Controversies and Considerations
Biology of reproduction, 2015Co-Authors: Siti Nornadhirah Amdani, Celine Jones, Marc Yeste, Kevin CowardAbstract:The beginning of embryogenesis is preceded by a sequence of events mediated by the release of intracellular calcium in the ooplasm, a multifaceted process known as Oocyte Activation. It is now well established that a sperm protein factor introduced into the Oocyte at the time of gamete fusion is responsible for initiating the cascade of signaling events involved. Several sperm proteins have been hypothesized as the sperm Oocyte-activating factor (SOAF) over the years, with phospholipase C zeta 1 (PLCZ1 or PLCzeta) emerging as the strongest candidate. A large body of consistent and reproducible evidence, from both biochemical and clinical settings, has accumulated in support of PLCzeta, and data clearly demonstrate that Oocyte Activation ability can be rescued in PLCzeta-deficient sperm by either PLCzeta cRNA or recombinant PLCzeta protein. However, a series of recent publications has challenged the dominance of PLCzeta and proposed an alternative candidate protein, WBP2 N-terminal like (WBP2NL or PAWP). These events have led to significant debate, fueled by the opposing views of two independent laboratories, each defending its own respective SOAF candidate. This raises important questions with regards to the relative importance of these two proteins in diagnostic and therapeutic medicine, and invites urgent research attention. Here, it is our intention to reflect upon this now very controversial area in order to engage the scientific and clinical communities in addressing the true importance of these two sperm proteins.
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Oocyte Activation and Phospholipase C Zeta (PLCζ): Male Infertility and Implications for Therapeutic Intervention
Phospholipases in Health and Disease, 2014Co-Authors: Junaid Kashir, Celine Jones, Kevin CowardAbstract:Infertility is a condition that now affects an estimated one in seven couples. In approximately 40 % of cases, the primary cause of infertility rests with male-derived factors associated with a variety of anatomical, physiological, and molecular deficiencies. In a proportion of such cases, the functional ability of sperm to successfully fertilise and activate the Oocyte is compromised. While assisted reproductive technology can successfully circumvent some of these issues via the application of artificial Oocyte-activating agents, there is significant ongoing debate as to whether these chemical agents should be replaced with an endogenous alternative. Phospholipase C zeta (PLCζ) is the sperm-specific protein responsible for activating the quiescent Oocyte following gamete fusion. Identified in a number of mammalian and non-mammalian organisms, PLCζ plays a fundamental role in the process of Oocyte Activation by inducing the controlled release of calcium in the ooplasm via an inositol triphosphate (IP3)-mediated signalling cascade. A growing body of evidence shows clear association between abnormalities in PLCζ structure, expression, localisation, and function to characterised states of human male infertility. Consequently there is significant global interest in PLCζ as both an endogenous therapeutic target to rescue infertile states associated with PLCζ-linked Oocyte Activation deficiency, and a diagnostic marker for Oocyte Activation ability. Here, we discuss the present status of PLCζ research and contemplate future applications of this fundamental sperm PLC in the clinic.
Kaoru Yanagida - One of the best experts on this subject based on the ideXlab platform.
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Clinical Application of Calcium Ionophore (A23187) Oocyte Activation in Fertilization Failure after ICSI
Journal of Mammalian Ova Research, 2015Co-Authors: Mami Enjoji, Miki Muroi, Satoru Takamizawa, Kaoru YanagidaAbstract:Abstract: Fertilization failure occurs in 1–5% of ICSI cases. An abnormality of the Oocyte activating ability of spermatozoa is one of a major causes of fertilization failure. For such cases, artificial Oocyte Activation (AOA) is expected as a method of treating for fertilization failure after ICSI. There are various methods of AOA combined with ICSI. We have adopted treatment with calcium ionophore, A23187, which is a commonly used method, and here, we report on the present status of the methods of Oocyte Activation combined with ICSI that we use. Although AOA with electrical technique or chemicals stimulation is clinically performed, the safety of this has not yet been proven, and the safer effective methods of AOA are desired.
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The Oocyte Activation and Ca2+ oscillation-inducing abilities of mouse and human dead (sonicated) spermatozoa.
Zygote (Cambridge England), 2009Co-Authors: Hiroyuki Yazawa, Kaoru Yanagida, Shoutaro Hayashi, Akira SatoAbstract:In ICSI procedures, it is well known that the selection of viable (live) spermatozoa and certain types of immobilization prior to injection is very important for obtaining successful results, but unfortunately there are rare situations when only immotile spermatozoa are available (such as in severe asthenozoospermia or necrozoospermia). In such cases, failure of Oocyte Activation after ICSI often occurs and may be due to the lack of SOAF (sperm-borne Oocyte activating factor) activity. In order to investigate the SOAF activities of dead spermatozoa, mouse and human spermatozoa were immobilized (killed by sonication), maintained in THF medium for varying time intervals (up to 72 h) and then injected into mature unfertilized mouse Oocytes. Injected mouse Oocytes were examined for their Activation, development into blastocysts and Ca 2+ responses by imaging and confocal laser scanning microscope. The rates of Oocyte Activation, blastocyst development and normal patterns of Ca 2+ oscillation from the killed-sperm-injected Oocytes decreased gradually in accordance with the maintenance interval between sonication and injection. For injection with mouse sonicated spermatozoa, the rate of normal Ca 2+ oscillations declined first (after a 3 h maintenance interval) and then blastocyst development was gradually obstructed (after approx. 10 h). The Oocyte Activation-inducing ability of dead spermatozoa was maintained for a relatively long period, but began to decline after 20 h. The Activation rates and Ca 2+ response of the Oocytes that were injected with human sonicated spermatozoa decreased earlier than those injected with mouse spermatozoa. Although the Oocyte Activation-inducing ability was maintained for a relatively long time after the death of the spermatozoa, embryo development into blastocysts and the rate of normal Ca 2+ oscillations declined after a short maintenance interval between sonication and injection. The Ca 2+ response seemed to be the most sensitive indicator for the evaluating the SOAF activity of dead (killed) spermatozoa.
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The present status of artificial Oocyte Activation in assisted reproductive technology
Reproductive medicine and biology, 2008Co-Authors: Kaoru Yanagida, Yoko Fujikura, Haruo KatayoseAbstract:Intracytoplasmic sperm injection (ICSI) is the most effective treatment for achieving fertilization in assisted reproductive technology (ART). However, fertilization failure occurs. The incidence of fertilization failure after ICSI is 1–5%. Approximately 50% of fertilization failure cases could be attributed to the abnormality of sperm factor. As the fertilization fails after ICSI using mature sperm, round spermatids and globozoospermia, artificial Oocyte Activation may provide a means of improving fertilization rates in such cases. The Oocyte Activation treatments used in clinical research include calcium (Ca) ionophore treatment, electrostimulation and strontium treatment. In terms of the efficiency of Oocyte Activation, electrostimulation and Ca ionophore gave better outcomes than strontium treatment. Strontium treatment causes Ca2+ oscillations in mice, so it has been viewed favorably. However, in human Oocytes calcium oscillation has not been observed. The fertilization rate after ICSI was low in the case of globozoospermia and wiht round spermatids. Some cases of pregnancy were achieved by ICSI alone and Oocyte Activation methods were not essential in these cases. Among the various Oocyte Activation methods currently used, it should be noted that issues of genetic safety have not been addressed for the combined use of these Oocyte Activation methods.
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Human round spermatids from azoospermic men exhibit Oocyte-Activation and Ca2+ oscillation-inducing activities.
Zygote (Cambridge England), 2007Co-Authors: H. Yazawa, Kaoru Yanagida, Akira SatoAbstract:During mammalian fertilization, intracellular Ca 2+ oscillations are important for both Oocyte Activation and embryonic development. As the ability of round spermatids (ROS) to induce Ca 2+ oscillations and Oocyte Activation is different between species, we examined Ca 2+ oscillation- and Oocyte Activation-inducing abilities of human ROS originating from patients with non-obstructive azoospermia. Human ROS from 11 non-obstructive azoospermic patients were collected during their TESE–ICSI cycles. Following injection into mature unfertilized mouse Oocytes, we examined the Oocyte-activating and Ca 2+ oscillation-inducing activities of ROS by using Ca 2+ imaging and confocal laser scanning microscopy (mouse test). In these 11 cases, clinical TESE–ICSI using mature testicular spermatozoa was successful, with the exception of one case in which only one sperm-injected Oocyte was not fertilized. The mean fertilization rate was 70.1% (40–100%); the mean cleavage rate was 97.9% (46/47). Two pregnancies were established from 10 transfer cycles (PR; 20%). When the ROS from these patients were injected into mouse Oocytes, the ROS from all patients induced at least some intracellular Ca 2+ oscillations (25–100%). In all patients, 40 out of 82 Oocytes injected with ROS exhibited normal oscillation patterns of [Ca 2+ ]i. Human spermatogenetic cells acquired Oocyte-activating and Ca 2+ oscillation-inducing abilities at the round spermatid stage, an earlier stage than found for rodent cells. These data indicate that human ROS might be useful for clinical treatments of non-obstructive azoospermic patients exhibiting mature spermatozoa in biopsied specimens.
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Successful pregnancy after ICSI with strontium Oocyte Activation in low rates of fertilization.
Reproductive biomedicine online, 2006Co-Authors: Kaoru Yanagida, Haruo Katayose, Syotaro Hayashi, Kazuto Morozumi, Akira SatoAbstract:Fertilization failure (complete fertilization failure or low fertilization rates) after intracytoplasmic sperm injection (ICSI) can occur in rare cases. In the majority of these cases, the unfertilized Oocytes are inactivated. Assisted Oocyte Activation was applied as a treatment option for a case of low fertilization rate as a clinical trial. A patient with a low fertilization rate (ranging from 0% to 33.3%; mean = 17.0%) after eight previous ICSI cycles at another hospital, was diagnosed with fertilization failure. The most likely cause of fertilization failure was failure of Oocyte Activation. Therefore, artificial Oocyte Activation by strontium treatment was combined with ICSI to achieve viable fertilized Oocytes. Oocytes were stimulated with strontium (10 mM SrCl(2), 60 min) approximately 30 min after ICSl. Six injected Oocytes were stimulated and all were then successfully fertilized. Two blastocysts were transferred into the uterus, resulting in a pregnancy and birth. A second pregnancy was achieved following implantation of two cryopreserved embryos (one blastocyst and one morula). In conclusion, strontium treatment was found to be an effective method for artificial Oocyte Activation in a case with a low fertilization rate after ICSI.
Junaid Kashir - One of the best experts on this subject based on the ideXlab platform.
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Functional disparity between human PAWP and PLCζ in the generation of Ca2+ oscillations for Oocyte Activation
Molecular human reproduction, 2015Co-Authors: Michail Nomikos, Junaid Kashir, Randa Sanusi, Jessica R. Sanders, Luke Buntwal, Daniel Love, Peter Ashley, David Sanders, Paul Knaggs, Adnan BunkheilaAbstract:Mammalian Oocyte Activation is mediated by cytosolic calcium (Ca2+) oscillations initiated upon delivery of a putative ‘sperm factor’ by the fertilizing sperm. Previous studies suggest the identity of this sperm factor as the testis-specific phospholipase C-zeta (PLCζ). Recently, a post-acrosomal sheath WW domain-binding protein (PAWP) has been proposed as an alternative sperm factor candidate, following a report that human PAWP protein and cRNA elicited Ca2+ oscillations in mouse and human Oocytes. Those Ca2+ oscillations were inhibited by a PAWP-derived peptide corresponding to a functional PPGY binding motif. Herein, using a series of human PAWP expression constructs, we demonstrate that both human PAWP protein and cRNA are, in our experiments, unable to elicit Ca2+ release following microinjection into mouse Oocytes. Parallel experiments performed with human PLCζ elicited the characteristic Ca2+ oscillations present at mammalian fertilization, which produced Oocyte Activation and embryo development. Furthermore, sperm-induced Ca2+ oscillations were not inhibited by the PAWP-derived PPGY peptide following in vitro fertilization or intracytoplasmic sperm injection. Thus, the functional disparity with PLCζ leads us to conclude that human PAWP is neither sufficient nor necessary for the Ca2+ oscillations that initiate mammalian Oocyte Activation at fertilization.
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Oocyte Activation and Phospholipase C Zeta (PLCζ): Male Infertility and Implications for Therapeutic Intervention
Phospholipases in Health and Disease, 2014Co-Authors: Junaid Kashir, Celine Jones, Kevin CowardAbstract:Infertility is a condition that now affects an estimated one in seven couples. In approximately 40 % of cases, the primary cause of infertility rests with male-derived factors associated with a variety of anatomical, physiological, and molecular deficiencies. In a proportion of such cases, the functional ability of sperm to successfully fertilise and activate the Oocyte is compromised. While assisted reproductive technology can successfully circumvent some of these issues via the application of artificial Oocyte-activating agents, there is significant ongoing debate as to whether these chemical agents should be replaced with an endogenous alternative. Phospholipase C zeta (PLCζ) is the sperm-specific protein responsible for activating the quiescent Oocyte following gamete fusion. Identified in a number of mammalian and non-mammalian organisms, PLCζ plays a fundamental role in the process of Oocyte Activation by inducing the controlled release of calcium in the ooplasm via an inositol triphosphate (IP3)-mediated signalling cascade. A growing body of evidence shows clear association between abnormalities in PLCζ structure, expression, localisation, and function to characterised states of human male infertility. Consequently there is significant global interest in PLCζ as both an endogenous therapeutic target to rescue infertile states associated with PLCζ-linked Oocyte Activation deficiency, and a diagnostic marker for Oocyte Activation ability. Here, we discuss the present status of PLCζ research and contemplate future applications of this fundamental sperm PLC in the clinic.
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variance in total levels of phospholipase c zeta plc ζ in human sperm may limit the applicability of quantitative immunofluorescent analysis as a diagnostic indicator of Oocyte Activation capability
Fertility and Sterility, 2013Co-Authors: Junaid Kashir, Petra De Sutter, Björn Heindryckx, Celine Jones, John Parrington, Walaa M Ramadan, Ginny Mounce, Bernadette Lemmon, Karen Turner, Tim ChildAbstract:Objective To examine whether similar levels of phospholipase C zeta (PLC-ζ) protein are present in sperm from men whose ejaculates resulted in normal Oocyte Activation, and to examine whether a predominant pattern of PLC-ζ localization is linked to normal Oocyte Activation ability. Design Laboratory study. Setting University laboratory. Patient(s) Control subjects (men with proven Oocyte Activation capacity; n=16) and men whose sperm resulted in recurrent intracytoplasmic sperm injection failure (Oocyte Activation deficient [OAD]; n=5). Intervention(s) Quantitative immunofluorescent analysis of PLC-ζ protein in human sperm. Main Outcome Measure(s) Total levels of PLC-ζ fluorescence, proportions of sperm exhibiting PLC-ζ immunoreactivity, and proportions of PLC-ζ localization patterns in sperm from control and OAD men. Result(s) Sperm from control subjects presented a significantly higher proportion of sperm exhibiting PLC-ζ immunofluorescence compared with infertile men diagnosed with OAD (82.6% and 27.4%, respectively). Total levels of PLC-ζ in sperm from individual control and OAD patients exhibited significant variance, with sperm from 10 out of 16 (62.5%) exhibiting levels similar to OAD samples. Predominant PLC-ζ localization patterns varied between control and OAD samples with no predictable or consistent pattern. Conclusion(s) The results indicate that sperm from control men exhibited significant variance in total levels of PLC-ζ protein, as well as significant variance in the predominant localization pattern. Such variance may hinder the diagnostic application of quantitative PLC-ζ immunofluorescent analysis.
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Oocyte Activation and phospholipase C zeta (PLCζ): diagnostic and therapeutic implications for assisted reproductive technology
Cell Communication and Signaling, 2012Co-Authors: Walaa M Ramadan, Junaid Kashir, Celine Jones, Kevin CowardAbstract:Infertility affects one in seven couples globally and has recently been classified as a disease by the World Health Organisation (WHO). While in-vitro fertilisation (IVF) offers effective treatment for many infertile couples, cases exhibiting severe male infertility (19–57%) often remain difficult, if not impossible to treat. In such cases, intracytoplasmic sperm injection (ICSI), a technique in which a single sperm is microinjected into the Oocyte, is implemented. However, 1–5% of ICSI cycles still fail to fertilise, affecting over 1000 couples per year in the UK alone. Pregnancy and delivery rates for IVF and ICSI rarely exceed 30% and 23% respectively. It is therefore imperative that Assisted Reproductive Technology (ART) protocols are constantly modified by associated research programmes, in order to provide patients with the best chances of conception. Prior to fertilisation, mature Oocytes are arrested in the metaphase stage of the second meiotic division (MII), which must be alleviated to allow the cell cycle, and subsequent embryogenesis, to proceed. Alleviation occurs through a series of concurrent events, collectively termed ‘ Oocyte Activation ’. In mammals, Oocytes are activated by a series of intracellular calcium (Ca^2+) oscillations following gamete fusion. Recent evidence implicates a sperm-specific phospholipase C, PLCzeta (PLCζ), introduced into the Oocyte following membrane fusion as the factor responsible. This review summarises our current understanding of Oocyte Activation failure in human males, and describes recent advances in our knowledge linking certain cases of male infertility with defects in PLCζ expression and activity. Systematic literature searches were performed using PubMed and the ISI-Web of Knowledge. Databases compiled by the United Nations and World Health Organisation databases (UNWHO), and the Human Fertilization and Embryology Authority (HFEA) were also scrutinised. It is clear that PLCζ plays a fundamental role in the Activation of mammalian Oocytes, and that genetic, molecular, or biochemical perturbation of this key enzyme is strongly linked to human infertility where Oocyte Activation is deficient. Consequently, there is significant scope for our understanding of PLCζ to be translated to the ART clinic, both as a novel therapeutic agent with which to rescue Oocyte Activation deficiency (OAD), or as a prognostic/diagnostic biomarker of Oocyte Activation ability in target sperm samples.
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Calcium oscillations, Oocyte Activation, and phospholipase C zeta.
Advances in experimental medicine and biology, 2012Co-Authors: Junaid Kashir, Celine Jones, Kevin CowardAbstract:In mammals, gamete fusion initiates a succession of oscillations in the intracellular concentration of calcium within the Oocyte, prompting a series of events to occur that are collectively known as “Oocyte Activation”. Such events are a fundamental necessity for the initiation of cell division and subsequent embryogenesis. Compelling evidence now indicates that these calcium oscillations are caused by a testis-specific phospholipase C (PLC) termed PLCzeta (PLCζ), released into the Oocyte following gamete fusion. A series of recent studies indicate that abnormal expression or aberrant activity of PLCζ is linked to certain types of human male infertility, where Oocyte Activation ability is impaired or absent altogether. In this chapter, we discuss the critical role of calcium oscillations in the process of Oocyte Activation, review the role of PLCs in this fundamental biological reaction, describe how PLCζ has been formally linked to male infertility, and postulate the potential roles for PLCζ in terms of clinical diagnosis and therapy.
