The Experts below are selected from a list of 28506 Experts worldwide ranked by ideXlab platform
Khaled Machaca - One of the best experts on this subject based on the ideXlab platform.
-
Ion Channel Function During Oocyte Maturation and Fertilization.
Frontiers in cell and developmental biology, 2018Co-Authors: Ingrid Carvacho, Matthias Piesche, Thorsten J. Maier, Khaled MachacaAbstract:The proper Maturation of both male and female gametes is essential for supporting fertilization and the early embryonic divisions. In the ovary, immature fully-grown Oocytes that are arrested in prophase I of meiosis I are not able to support fertilization. Acquiring fertilization competence requires resumption of meiosis which encompasses the remodeling of multiple signaling pathways and the reorganization of cellular organelles. Collectively, this differentiation endows the egg with the ability to activate at fertilization and to promote the egg-to-embryo transition. Oocyte Maturation is associated with changes in the electrical properties of the plasma membrane and alterations in the function and distribution of ion channels. Therefore, variations on the pattern of expression, distribution, and function of ion channels and transporters during Oocyte Maturation are fundamental to reproductive success. Ion channels and transporters are important in regulating membrane potential, but also in the case of calcium (Ca2+), they play a critical role in modulating intracellular signaling pathways. In the context of fertilization, Ca2+ has been shown to be the universal activator of development at fertilization, playing a central role in early events associated with egg activation and the egg-to-embryo transition. These early events include the block of polyspermy, the completion of meiosis and the transition to the embryonic mitotic divisions. In this review, we discuss the role of ion channels during Oocyte Maturation, fertilization and early embryonic development. We will describe how ion channel studies in Xenopus Oocytes, an extensively studied model of Oocyte Maturation, translate into a greater understanding of the role of ion channels in mammalian Oocyte physiology.
-
Internalization of plasma membrane Ca2+-ATPase during Xenopus Oocyte Maturation
Developmental biology, 2008Co-Authors: Wassim El-jouni, Shirley Haun, Khaled MachacaAbstract:A transient increase in intracellular Ca2+ is the universal signal for egg activation at fertilization. Eggs acquire the ability to mount the specialized fertilization-specific Ca2+ signal during Oocyte Maturation. The first Ca2+ transient following sperm entry in vertebrate eggs has a slow rising phase followed by a sustained plateau. The molecular determinants of the sustained plateau are poorly understood. We have recently shown that a critical determinant of Ca2+ signaling differentiation during Oocyte Maturation is internalization of the plasma membrane calcium ATPase (PMCA). PMCA internalization is representative of endocytosis of several integral membrane proteins during Oocyte Maturation, a requisite process for early embryogenesis. Here we investigate the mechanisms regulating PMCA internalization. To track PMCA trafficking in live cells we cloned a full-length cDNA of Xenopus PMCA1, and show that GFP-tagged PMCA traffics in a similar fashion to endogenous PMCA. Functional data show that MPF activation during Oocyte Maturation is required for full PMCA internalization. Pharmacological and co-localization studies argue that PMCA is internalized through a lipid raft endocytic pathway. Deletion analysis reveal a requirement for the N-terminal cytoplasmic domain for efficient internalization. Together these studies define the mechanistic requirements for PMCA internalization during Oocyte Maturation.
-
Ca2+ Homeostasis Regulates Xenopus Oocyte Maturation
Biology of reproduction, 2007Co-Authors: Lu Sun, Shirley Haun, Rawad Hodeify, Amanda Charlesworth, Angus M. Macnicol, Subramaniam Ponnappan, Usha Ponnappan, Claude Prigent, Khaled MachacaAbstract:In contrast to the well-defined role of Ca 2+ signals during mitosis, the contribution of Ca 2+ signaling to meiosis progression is controversial, despite several decades of investigating the role of Ca 2+ and its effectors in vertebrate Oocyte Maturation. We have previously shown that during Xenopus Oocyte Maturation, Ca 2+ signals are dispensable for entry into meiosis and for germinal vesicle breakdown. However, normal Ca 2+ homeostasis is essential for completion of meiosis I and extrusion of the first polar body. In this study, we test the contribution of several downstream effectors in mediating the Ca 2+ effects during Oocyte Maturation. We show that calmodulin and calcium-calmodulin-dependent protein kinase II (CAMK2) are not critical downstream Ca 2+ effectors during meiotic Maturation. In contrast, accumulation of Aurora kinase A (AURKA) protein is disrupted in cells deprived of Ca 2+ signals. Since AURKA is required for bipolar spindle formation, failure to accumulate AURKA may contribute to the defective spindle phenotype following Ca 2+ deprivation. These findings argue that Ca 2+ homeostasis is important in establishing the Oocyte’s competence to undergo Maturation in preparation for fertilization and embryonic development.
-
Ca2+ signaling differentiation during Oocyte Maturation
Journal of cellular physiology, 2007Co-Authors: Khaled MachacaAbstract:Oocyte Maturation is an essential cellular differentiation pathway that prepares the egg for activation at fertilization leading to the initiation of embryogenesis. An integral attribute of Oocyte Maturation is the remodeling of Ca2+ signaling pathways endowing the egg with the capacity to produce a specialized Ca2+ transient at fertilization that is necessary and sufficient for egg activation. Consequently, mechanistic elucidation of Ca2+ signaling differentiation during Oocyte Maturation is fundamental to our understanding of egg activation, and offers a glimpse into Ca2+ signaling regulation during the cell cycle.
-
Calcium signaling differentiation during Xenopus Oocyte Maturation.
Developmental biology, 2005Co-Authors: Wassim El-jouni, Byungwoo Jang, Shirley Haun, Khaled MachacaAbstract:Ca 2+ is the universal signal for egg activation at fertilization in all sexually reproducing species. The Ca 2+ signal at fertilization is necessary for egg activation and exhibits specialized spatial and temporal dynamics. Eggs acquire the ability to produce the fertilization-specific Ca 2+ signal during Oocyte Maturation. However, the mechanisms regulating Ca 2+ signaling differentiation during Oocyte Maturation remain largely unknown. At fertilization, Xenopus eggs produce a cytoplasmic Ca 2+ (Ca 2+) rise that lasts for several minutes, and is required for egg activation. Here, we show that during Oocyte Maturation Ca 2+ transport effectors are tightly modulated. The plasma membrane Ca 2+ ATPase (PMCA) is completely internalized during Maturation, and is therefore unable to extrude Ca 2+ out of the cell. Furthermore, IP3-dependent Ca 2+ release is required for the sustained Ca 2+ rise in eggs, showing that Ca 2+ that is pumped into the ER leaks back out through IP3 receptors. This apparent futile cycle allows eggs to maintain elevated cytoplasmic Ca 2+ despite the limited available Ca 2+ in intracellular stores. Therefore, Ca 2+ signaling differentiates in a highly orchestrated fashion during Xenopus Oocyte Maturation endowing the egg with the capacity to produce a sustained Ca 2+ transient at
Mika Tokumoto - One of the best experts on this subject based on the ideXlab platform.
-
In vivo induction of Oocyte Maturation and ovulation in zebrafish
PLoS ONE, 2011Co-Authors: Toshinobu Tokumoto, Toshiya Yamaguchi, Mika TokumotoAbstract:The Maturation of fish Oocytes is a well-characterized system induced by progestins via non-genomic actions. In a previous study, we demonstrated that diethylstilbestrol (DES), a non-steroidal estrogen, induces fish Oocyte Maturation via the membrane progestin receptor (mPR). Here, we attempted to evaluate the effect of DES as an environmental endocrine disrupting chemical (EDC) upon fish Oocyte Maturation using live zebrafish. DES triggered Oocyte Maturation within several hours in vivo when administrated directly into the surrounding water. The natural teleost Maturation-inducing hormone, 17alpha, 20beta-dihydroxy-4-pregnen-3-one (17,20beta-DHP) also induced Oocyte Maturation in vivo. Steroids such as testosterone, progesterone or 17alpha-hydroxyprogesterone were also effective in vivo. Further studies indicated that externally applied 17,20beta-DHP even induced ovulation. In contrast to 17,20beta -DHP, DES induced Maturation but not ovulation. Theoretically this assay system provides a means to distinguish pathways involved in the induction of ovulation, which are known to be induced by genomic actions from the pathway normally involved in the induction of Oocyte Maturation, a typical non-genomic action-dependent pathway. In summary, we have demonstrated the effect of EDCs on fish Oocyte Maturation in vivo. To address the effects, we have explored a conceptually new approach to distinguish between the genomic and non-genomic actions induced by steroids. The assay can be applied to screens of progestin-like effects upon Oocyte Maturation and ovulation for small molecules of pharmacological agents or EDCs.
-
Induction and inhibition of Oocyte Maturation by EDCs in zebrafish
Reproductive biology and endocrinology : RB&E, 2005Co-Authors: Toshinobu Tokumoto, Mika Tokumoto, Yoshitaka NagahamaAbstract:Background: Oocyte Maturation in lower vertebrates is triggered by Maturation-inducing hormone (MIH), which acts on unidentified receptors on the Oocyte surface and induces the activation of Maturation-promoting factor (MPF) in the Oocyte cytoplasm. We previously described the induction of Oocyte Maturation in fish by an endocrine-disrupting chemical (EDC), diethylstilbestrol (DES), a nonsteroidal estrogen. Methods: In this study, stimulatory and inhibitory effects of EDCs and natural steroids on Oocyte Maturation were examined in zebrafish. For effective agents, some details about the mechanism in induction or inhibition of Maturation were examined. Possible groups of DES interacting with the MIH receptor are discussed based on relative potency of steroids to induce Maturation. Results: Among agents tested, tamoxifen (TAM) and its metabolite 4-hydroxytamoxifen (4-OHT) showed stimulatory activity similar to DES. The time courses of the change in germinal vesicle breakdown and an intracellular molecular event (the synthesis of cyclin B) induced by TAM were indistinguishable from those induced by MIH. In contrast, pentachlorophenol (PCP) had a potent inhibitory effect on MIH-induced Oocyte Maturation. PCP inhibited not only MIH-induced Maturation but also DES- and TAM-induced Maturation. Methoxychlor also inhibited Maturation when Oocytes were pre-treated with this agent. Conclusion: These results suggest that EDCs act as agonists or antagonists in the induction of Oocyte Maturation in fish.
-
diethylstilbestrol induces fish Oocyte Maturation
Proceedings of the National Academy of Sciences of the United States of America, 2004Co-Authors: Toshinobu Tokumoto, Mika Tokumoto, Ryo Horiguchi, Katsutoshi Ishikawa, Yoshitaka NagahamaAbstract:An endocrine-disrupting chemical, diethylstilbestrol (DES), a nonsteroidal estrogen, triggers Oocyte Maturation in fish. The morphology (the time course of the change in germinal vesicle breakdown) and an intracellular molecular event (the de novo synthesis of cyclin B) induced by DES were indistinguishable from those induced by a natural Maturation-inducing hormone, 17α,20β-dihydroxy-4-pregnen-3-one (17,20β-DHP). A synergistic action of DES on 17,20β-DHP-induced Oocyte Maturation was observed. Both 17,20β-DHP- and DES-induced Oocyte Maturation was inhibited by an antibody against the Maturation-inducing hormone receptor. The structural requirement for the action of DES is discussed based on results obtained with DES analogs.
Toshinobu Tokumoto - One of the best experts on this subject based on the ideXlab platform.
-
In vivo induction of Oocyte Maturation and ovulation in zebrafish
PLoS ONE, 2011Co-Authors: Toshinobu Tokumoto, Toshiya Yamaguchi, Mika TokumotoAbstract:The Maturation of fish Oocytes is a well-characterized system induced by progestins via non-genomic actions. In a previous study, we demonstrated that diethylstilbestrol (DES), a non-steroidal estrogen, induces fish Oocyte Maturation via the membrane progestin receptor (mPR). Here, we attempted to evaluate the effect of DES as an environmental endocrine disrupting chemical (EDC) upon fish Oocyte Maturation using live zebrafish. DES triggered Oocyte Maturation within several hours in vivo when administrated directly into the surrounding water. The natural teleost Maturation-inducing hormone, 17alpha, 20beta-dihydroxy-4-pregnen-3-one (17,20beta-DHP) also induced Oocyte Maturation in vivo. Steroids such as testosterone, progesterone or 17alpha-hydroxyprogesterone were also effective in vivo. Further studies indicated that externally applied 17,20beta-DHP even induced ovulation. In contrast to 17,20beta -DHP, DES induced Maturation but not ovulation. Theoretically this assay system provides a means to distinguish pathways involved in the induction of ovulation, which are known to be induced by genomic actions from the pathway normally involved in the induction of Oocyte Maturation, a typical non-genomic action-dependent pathway. In summary, we have demonstrated the effect of EDCs on fish Oocyte Maturation in vivo. To address the effects, we have explored a conceptually new approach to distinguish between the genomic and non-genomic actions induced by steroids. The assay can be applied to screens of progestin-like effects upon Oocyte Maturation and ovulation for small molecules of pharmacological agents or EDCs.
-
Induction and inhibition of Oocyte Maturation by EDCs in zebrafish
Reproductive biology and endocrinology : RB&E, 2005Co-Authors: Toshinobu Tokumoto, Mika Tokumoto, Yoshitaka NagahamaAbstract:Background: Oocyte Maturation in lower vertebrates is triggered by Maturation-inducing hormone (MIH), which acts on unidentified receptors on the Oocyte surface and induces the activation of Maturation-promoting factor (MPF) in the Oocyte cytoplasm. We previously described the induction of Oocyte Maturation in fish by an endocrine-disrupting chemical (EDC), diethylstilbestrol (DES), a nonsteroidal estrogen. Methods: In this study, stimulatory and inhibitory effects of EDCs and natural steroids on Oocyte Maturation were examined in zebrafish. For effective agents, some details about the mechanism in induction or inhibition of Maturation were examined. Possible groups of DES interacting with the MIH receptor are discussed based on relative potency of steroids to induce Maturation. Results: Among agents tested, tamoxifen (TAM) and its metabolite 4-hydroxytamoxifen (4-OHT) showed stimulatory activity similar to DES. The time courses of the change in germinal vesicle breakdown and an intracellular molecular event (the synthesis of cyclin B) induced by TAM were indistinguishable from those induced by MIH. In contrast, pentachlorophenol (PCP) had a potent inhibitory effect on MIH-induced Oocyte Maturation. PCP inhibited not only MIH-induced Maturation but also DES- and TAM-induced Maturation. Methoxychlor also inhibited Maturation when Oocytes were pre-treated with this agent. Conclusion: These results suggest that EDCs act as agonists or antagonists in the induction of Oocyte Maturation in fish.
-
diethylstilbestrol induces fish Oocyte Maturation
Proceedings of the National Academy of Sciences of the United States of America, 2004Co-Authors: Toshinobu Tokumoto, Mika Tokumoto, Ryo Horiguchi, Katsutoshi Ishikawa, Yoshitaka NagahamaAbstract:An endocrine-disrupting chemical, diethylstilbestrol (DES), a nonsteroidal estrogen, triggers Oocyte Maturation in fish. The morphology (the time course of the change in germinal vesicle breakdown) and an intracellular molecular event (the de novo synthesis of cyclin B) induced by DES were indistinguishable from those induced by a natural Maturation-inducing hormone, 17α,20β-dihydroxy-4-pregnen-3-one (17,20β-DHP). A synergistic action of DES on 17,20β-DHP-induced Oocyte Maturation was observed. Both 17,20β-DHP- and DES-induced Oocyte Maturation was inhibited by an antibody against the Maturation-inducing hormone receptor. The structural requirement for the action of DES is discussed based on results obtained with DES analogs.
Yoshitaka Nagahama - One of the best experts on this subject based on the ideXlab platform.
-
Induction and inhibition of Oocyte Maturation by EDCs in zebrafish
Reproductive biology and endocrinology : RB&E, 2005Co-Authors: Toshinobu Tokumoto, Mika Tokumoto, Yoshitaka NagahamaAbstract:Background: Oocyte Maturation in lower vertebrates is triggered by Maturation-inducing hormone (MIH), which acts on unidentified receptors on the Oocyte surface and induces the activation of Maturation-promoting factor (MPF) in the Oocyte cytoplasm. We previously described the induction of Oocyte Maturation in fish by an endocrine-disrupting chemical (EDC), diethylstilbestrol (DES), a nonsteroidal estrogen. Methods: In this study, stimulatory and inhibitory effects of EDCs and natural steroids on Oocyte Maturation were examined in zebrafish. For effective agents, some details about the mechanism in induction or inhibition of Maturation were examined. Possible groups of DES interacting with the MIH receptor are discussed based on relative potency of steroids to induce Maturation. Results: Among agents tested, tamoxifen (TAM) and its metabolite 4-hydroxytamoxifen (4-OHT) showed stimulatory activity similar to DES. The time courses of the change in germinal vesicle breakdown and an intracellular molecular event (the synthesis of cyclin B) induced by TAM were indistinguishable from those induced by MIH. In contrast, pentachlorophenol (PCP) had a potent inhibitory effect on MIH-induced Oocyte Maturation. PCP inhibited not only MIH-induced Maturation but also DES- and TAM-induced Maturation. Methoxychlor also inhibited Maturation when Oocytes were pre-treated with this agent. Conclusion: These results suggest that EDCs act as agonists or antagonists in the induction of Oocyte Maturation in fish.
-
diethylstilbestrol induces fish Oocyte Maturation
Proceedings of the National Academy of Sciences of the United States of America, 2004Co-Authors: Toshinobu Tokumoto, Mika Tokumoto, Ryo Horiguchi, Katsutoshi Ishikawa, Yoshitaka NagahamaAbstract:An endocrine-disrupting chemical, diethylstilbestrol (DES), a nonsteroidal estrogen, triggers Oocyte Maturation in fish. The morphology (the time course of the change in germinal vesicle breakdown) and an intracellular molecular event (the de novo synthesis of cyclin B) induced by DES were indistinguishable from those induced by a natural Maturation-inducing hormone, 17α,20β-dihydroxy-4-pregnen-3-one (17,20β-DHP). A synergistic action of DES on 17,20β-DHP-induced Oocyte Maturation was observed. Both 17,20β-DHP- and DES-induced Oocyte Maturation was inhibited by an antibody against the Maturation-inducing hormone receptor. The structural requirement for the action of DES is discussed based on results obtained with DES analogs.
Wassim El-jouni - One of the best experts on this subject based on the ideXlab platform.
-
Internalization of plasma membrane Ca2+-ATPase during Xenopus Oocyte Maturation
Developmental biology, 2008Co-Authors: Wassim El-jouni, Shirley Haun, Khaled MachacaAbstract:A transient increase in intracellular Ca2+ is the universal signal for egg activation at fertilization. Eggs acquire the ability to mount the specialized fertilization-specific Ca2+ signal during Oocyte Maturation. The first Ca2+ transient following sperm entry in vertebrate eggs has a slow rising phase followed by a sustained plateau. The molecular determinants of the sustained plateau are poorly understood. We have recently shown that a critical determinant of Ca2+ signaling differentiation during Oocyte Maturation is internalization of the plasma membrane calcium ATPase (PMCA). PMCA internalization is representative of endocytosis of several integral membrane proteins during Oocyte Maturation, a requisite process for early embryogenesis. Here we investigate the mechanisms regulating PMCA internalization. To track PMCA trafficking in live cells we cloned a full-length cDNA of Xenopus PMCA1, and show that GFP-tagged PMCA traffics in a similar fashion to endogenous PMCA. Functional data show that MPF activation during Oocyte Maturation is required for full PMCA internalization. Pharmacological and co-localization studies argue that PMCA is internalized through a lipid raft endocytic pathway. Deletion analysis reveal a requirement for the N-terminal cytoplasmic domain for efficient internalization. Together these studies define the mechanistic requirements for PMCA internalization during Oocyte Maturation.
-
Calcium signaling differentiation during Xenopus Oocyte Maturation.
Developmental biology, 2005Co-Authors: Wassim El-jouni, Byungwoo Jang, Shirley Haun, Khaled MachacaAbstract:Ca 2+ is the universal signal for egg activation at fertilization in all sexually reproducing species. The Ca 2+ signal at fertilization is necessary for egg activation and exhibits specialized spatial and temporal dynamics. Eggs acquire the ability to produce the fertilization-specific Ca 2+ signal during Oocyte Maturation. However, the mechanisms regulating Ca 2+ signaling differentiation during Oocyte Maturation remain largely unknown. At fertilization, Xenopus eggs produce a cytoplasmic Ca 2+ (Ca 2+) rise that lasts for several minutes, and is required for egg activation. Here, we show that during Oocyte Maturation Ca 2+ transport effectors are tightly modulated. The plasma membrane Ca 2+ ATPase (PMCA) is completely internalized during Maturation, and is therefore unable to extrude Ca 2+ out of the cell. Furthermore, IP3-dependent Ca 2+ release is required for the sustained Ca 2+ rise in eggs, showing that Ca 2+ that is pumped into the ER leaks back out through IP3 receptors. This apparent futile cycle allows eggs to maintain elevated cytoplasmic Ca 2+ despite the limited available Ca 2+ in intracellular stores. Therefore, Ca 2+ signaling differentiates in a highly orchestrated fashion during Xenopus Oocyte Maturation endowing the egg with the capacity to produce a sustained Ca 2+ transient at
