Hypoxic microenvironment within an embryo induces apoptosis and is essential for proper morphological development

Chen, Eric; Fujinaga, Masahiko; Giaccia, Amato J.

doi:10.1002/(sici)1096-9926(199910)60:4<215::aid-tera6>3.0.co;2-2

Cited by 106 publications

(48 citation statements)

References 43 publications

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“…The placenta receives nutrients, oxygen, antibodies and hormones from the mother’s blood and passes out waste (Hanson, 2007). The oxygen requirements in rodent embryos vary during embryo development (Chen et al., 1999). Embryonic and placental cells are sensitive to oxidative stress because of their extensive cell divisions and the concomitant exposure of their DNA (Burton et al., 2003).…”

Section: Resultsmentioning

confidence: 99%

“…In mice, between approximately ED 9.5 and ED 11, the yolk sac of the placenta regresses and the definitive allantois in placenta provides for nutrition and respiratory exchange. This results in acute exposure to higher oxygen concentrations in the embryo (Chen et al., 1999; Feil et al., 2006). According to previous report, GI‐GPx has approximately 65% amino acid sequence identity and 60% nucleotide sequence identity with cGPx.…”

Section: Resultsmentioning

confidence: 99%

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Differential Expression of Gastrointestinal Glutathione Peroxidase (GI-GPx) Gene during Mouse Organogenesis

Baek

Yon

Lee

et al. 2011

Anatomia, Histologia, Embryologia

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Gastrointestinal glutathione peroxidase (GI-GPx) is an antioxidant enzyme that has been known to be restricted to the gastrointestinal tract in rodents. In an effort to determine the expression pattern of GI-GPx mRNA during organogenesis, quantitative real-time PCR and in situ hybridization for GI-GPx mRNA were conducted in whole embryos or each developing organ of mice. GI-GPx mRNA was expressed more abundantly in the extraembryonic tissues, including placenta than in embryos on embryonic days (EDs) 7.5-18.5 (P < 0.05). When compared with the expression levels of cytosolic GPx (cGPx) mRNA, GI-GPx mRNA levels were low in the embryos, but relatively high in the extraembryonic tissues (P < 0.05). According to the results of whole mount in situ hybridizations, GI-GPx mRNA was principally expressed in the ectoplacental cone, neural tube and fold, and primitive heart at EDs 7.5-8.5. At EDs 9.5-12.5, GI-GPx mRNA was abundantly expressed in nervous tissues such as the telencephalon, mesencephalon and dorsal neural tube and was also detected in the forelimb and hindlimb at EDs 10.5-12.5. In the sectioned embryos after ED 13.5, GI-GPx mRNA levels were high in the cerebral cortex, metanephric corpuscle, pancreatic ducts, surface epithelia of the skin, inner ear, and nasal conchae, gastrointestinal tract, liver, urinary bladder, airway passages of lung, and whisker follicles. These findings indicate that GI-GPx is not only spatiotemporally expressed in a variety of embryonic organs during organogenesis but also may perform a mutual compensatory role with the cGPx in the protection of embryos and extraembryonic tissues against the reactive oxygen species generated in ontogenetic periods.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Differential Expression of Gastrointestinal Glutathione Peroxidase (GI-GPx) Gene during Mouse Organogenesis

Baek

Yon

Lee

et al. 2011

Anatomia, Histologia, Embryologia

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“…The modifications often lead to cellular dysfunction and may have deleterious consequences. Dysregulations in the redox equilibrium induce developmental retardations, organ malformations, teratogenesis, and even embryo lethality (Chen et al, 1999; Hansen, 2006). The processes controlling embryonic redox homeostasis are important determinants of teratological risk.…”

Section: Embryo Developmentmentioning

confidence: 99%

The roles of glutathione peroxidases during embryo development

Ufer

Wang

2011

Front. Mol. Neurosci.

104

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Embryo development relies on the complex interplay of the basic cellular processes including proliferation, differentiation, and apoptotic cell death. Precise regulation of these events is the basis for the establishment of embryonic structures and the organ development. Beginning with fertilization of the oocyte until delivery the developing embryo encounters changing environmental conditions such as varying levels of oxygen, which can give rise to reactive oxygen species (ROS). These challenges are met by the embryo with metabolic adaptations and by an array of anti-oxidative mechanisms. ROS can be deleterious by modifying biological molecules including lipids, proteins, and nucleic acids and may induce abnormal development or even embryonic lethality. On the other hand ROS are vital players of various signaling cascades that affect the balance between cell growth, differentiation, and death. An imbalance or dysregulation of these biological processes may generate cells with abnormal growth and is therefore potentially teratogenic and tumorigenic. Thus, a precise balance between processes generating ROS and those decomposing ROS is critical for normal embryo development. One tier of the cellular protective system against ROS constitutes the family of selenium-dependent glutathione peroxidases (GPx). These enzymes reduce hydroperoxides to the corresponding alcohols at the expense of reduced glutathione. Of special interest within this protein family is the moonlighting enzyme glutathione peroxidase 4 (Gpx4). This enzyme is a scavenger of lipophilic hydroperoxides on one hand, but on the other hand can be transformed into an enzymatically inactive cellular structural component. GPx4 deficiency – in contrast to all other GPx family members – leads to abnormal embryo development and finally produces a lethal phenotype in mice. This review is aimed at summarizing the current knowledge on GPx isoforms during embryo development and tumor development with an emphasis on GPx4.

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“…The direct evidences about oxygen niche of embryonic neurogenesis were provided by Chen (Chen et al, 1999), utilizing the hypoxia marker EF5, a nitroimidazole derivative which binds covalently to protein, RNA, and DNA in cells exposed to a hypoxic environment (0.076–7.6 mmHg oxygen; Lord et al, 1993). They found that the neural tube in both the hindbrain and midbrain regions also stained strongly with the EF5 immunoreactivity, indicating that the oxygen tensions of these regions substantially below 7.6 mmHg (Lord et al, 1993).…”

Section: Oxygen Niche During Embryonic and Adult Neurogenesismentioning

confidence: 99%

“…However, the oxygen levels in almost all the regions of brain are very low: 32 ± 4 mmHg in the thalamus, 27 ± 6 mmHg in the cerebral cortex, 20 ± 3 mmHg in the hippocampus, and 15 ± 3 mmHg in the corpus callous in isoflurane-anesthetized rats (Ivanovic, 2009). In addition, the development of various organs of embryos including the central nervous system (CNS) takes place in low-oxygen concentration (Fischer and Bavister, 1993; Chen et al, 1999). Apart from this, oxygen levels in brain tissues are often altered during stroke (Liu et al, 2004), brain trauma (Valadka et al, 1998), and in the hyperbaric oxygen (HBO) environment (Balenane, 1982).…”

Section: Introductionmentioning

confidence: 99%

Oxygen, a Key Factor Regulating Cell Behavior during Neurogenesis and Cerebral Diseases

Zhang¹,

Zhu²,

Fan³

2011

Front. Mol. Neurosci.

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Oxygen is vital to maintain the normal functions of almost all the organs, especially for brain which is one of the heaviest oxygen consumers in the body. The important roles of oxygen on the brain are not only reflected in the development, but also showed in the pathological processes of many cerebral diseases. In the current review, we summarized the oxygen levels in brain tissues tested by real-time measurements during the embryonic and adult neurogenesis, the cerebral diseases, or in the hyperbaric/hypobaric oxygen environment. Oxygen concentration is low in fetal brain (0.076–7.6 mmHg) and in adult brain (11.4–53.2 mmHg), decreased during stroke, and increased in hyperbaric oxygen environment. In addition, we reviewed the effects of oxygen tensions on the behaviors of neural stem cells (NSCs) in vitro cultures at different oxygen concentration (15.2–152 mmHg) and in vivo niche during different pathological states and in hyperbaric/hypobaric oxygen environment. Moderate hypoxia (22.8–76 mmHg) can promote the proliferation of NSCs and enhance the differentiation of NSCs into the TH-positive neurons. Next, we briefly presented the oxygen-sensitive molecular mechanisms regulating NSCs proliferation and differentiation recently found including the Notch, Bone morphogenetic protein and Wnt pathways. Finally, the future perspectives about the roles of oxygen on brain and NSCs were given.

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Hypoxic microenvironment within an embryo induces apoptosis and is essential for proper morphological development

Cited by 106 publications

References 43 publications

Differential Expression of Gastrointestinal Glutathione Peroxidase (GI-GPx) Gene during Mouse Organogenesis

Differential Expression of Gastrointestinal Glutathione Peroxidase (GI-GPx) Gene during Mouse Organogenesis

The roles of glutathione peroxidases during embryo development

Oxygen, a Key Factor Regulating Cell Behavior during Neurogenesis and Cerebral Diseases

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