Effect of in vitro embryo culture and embryo transfer on global expression profiling of the fetal lung tissue in mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE101054 | GEO | 2018/05/01
REPOSITORIES: GEO
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Project description:This series compares the effects that two pharmacologically distinct ligands at the mitochondrial peripheral-type benzodiazepine receptor (Bzrp) has on gene expression in early mouse embryos cultured under different oxygen levels. Mouse embryos averaging 16-18 somite pairs were explanted on 9 d.p.c. and grown in culture under optimal oxygenation (21% oxygen, hyperbaric with respect to arterial blood = 80-100 mmHg). Most embryos (>90%) develop normally in over a 24h culture period. When embryos receive suboptimal oxygenation for 2.0h (5% oxygen, similar to venous blood = 38-40 mmHg) a high percentage of them (>60%) go on to develop abnormally or else fail. These hypoxic embryos are remediated with 5 uM PK11195 to ~25% malformation rate. Cultured embryos were exposed to different oxygen levels (5% or 21%) in the presence of the Bzrp ligands PK11195 (Bzrp antagonist) versus Ro5-4864 (Bzrp agonist). The sampling time was guided by p53 protein induction with hypoxia, and remediation with PK11195, at 4.0h of culture and exposures. Thus all measurements were on RNA from the prosencephalon collected 2.0h after start of the test period on 9 d.p.c. Keywords = peripheral benzodiazepine receptor Keywords = oxygen sensing Keywords = Bzrp ligands Keywords = PK11195 Keywords = Ro5-4864 Keywords = embryo Keywords = p53 protein induction
2010-06-09 | E-GEOD-1079 | biostudies-arrayexpress
Project description:This series compares the effects that two pharmacologically distinct ligands at the mitochondrial peripheral-type benzodiazepine receptor (Bzrp) has on gene expression in early mouse embryos cultured under different oxygen levels. Mouse embryos averaging 16-18 somite pairs were explanted on 9 d.p.c. and grown in culture under optimal oxygenation (21% oxygen, hyperbaric with respect to arterial blood = 80-100 mmHg). Most embryos (>90%) develop normally in over a 24h culture period. When embryos receive suboptimal oxygenation for 2.0h (5% oxygen, similar to venous blood = 38-40 mmHg) a high percentage of them (>60%) go on to develop abnormally or else fail. These hypoxic embryos are remediated with 5 uM PK11195 to ~25% malformation rate. Cultured embryos were exposed to different oxygen levels (5% or 21%) in the presence of the Bzrp ligands PK11195 (Bzrp antagonist) versus Ro5-4864 (Bzrp agonist). The sampling time was guided by p53 protein induction with hypoxia, and remediation with PK11195, at 4.0h of culture and exposures. Thus all measurements were on RNA from the prosencephalon collected 2.0h after start of the test period on 9 d.p.c. Keywords = peripheral benzodiazepine receptor Keywords = oxygen sensing Keywords = Bzrp ligands Keywords = PK11195 Keywords = Ro5-4864 Keywords = embryo Keywords = p53 protein induction Keywords: ordered
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Project description:This series compares the effects that two pharmacologically distinct ligands at the mitochondrial peripheral-type benzodiazepine receptor (Bzrp). PK11195 (4.0 mg/kg, a presumed antagonist) has no observable adverse effects in pregnant mice on either 8 days post-coitus (d.p.c.) or 9 d.p.c. Furthermore, PK11195 is shown to rescue mouse fetuses from microphthalmia or microphthalmia-microcephaly induced with 2CdA or MeHg, respectively; effects of PK11195 on EtOH-induced craniofacial malformations are not yet unkown. Ro5-4864 (4.0 mg/kg, a presumed agonist) is weakly teratogenic on 8 d.p.c. (effects on 9 d.p.c. unknown) and this Bzrp ligand does not rescue fetuses from malformations induced with either 2CdA or MeHg; effects of Ro5-4864 on EtOH-induced craniofacial malformations is unknown for either sensitive (C57BL/6J) or insensitive (C57BL/6N) strains. The 4.0 mg/kg dose of Bzrp ligands is consistent with pharmacological activity in several studies. Pregnant mice were exposed to these agents on 8 d.p.c. (2CdA, EtOH) or 9 d.p.c. (MeHg). The test dose of 2.5 mg/kg 2CdA was modeled for a 5% increased risk of microphthalmia in term fetuses. Full remediation with PK11195 anticipated. The test dose of 5.0 mg/kg MeHg gives an estimated 20% increased risk of microphthalmia-microcephaly (encephalopathy) in term fetuses. Partial remediation with PK11195 is anticipated to <10% malformations. Again the effects of PK11195 on EtOH teratogenicity is not yet known. The sampling time was chosen as the time of p53 protein induction (3.0h to 4.5h post-treatment). Whereas co-treatment with PK11195 suppresses embryonic p53 protein induction Ro5-4864 does not block this reaction. All measurements were on RNA from the embryonic headfold (8 d.p.c.) or prosencephalon (9 d.p.c.). Keywords = peripheral benzodiazepine receptor Keywords = Bzrp ligands Keywords = PK11195 Keywords = Ro5-4864 Keywords = embryo Keywords = p53 protein induction
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Project description:This series compares the effects that two pharmacologically distinct ligands at the mitochondrial peripheral-type benzodiazepine receptor (Bzrp). PK11195 (4.0 mg/kg, a presumed antagonist) has no observable adverse effects in pregnant mice on either 8 days post-coitus (d.p.c.) or 9 d.p.c. Furthermore, PK11195 is shown to rescue mouse fetuses from microphthalmia or microphthalmia-microcephaly induced with 2CdA or MeHg, respectively; effects of PK11195 on EtOH-induced craniofacial malformations are not yet unkown. Ro5-4864 (4.0 mg/kg, a presumed agonist) is weakly teratogenic on 8 d.p.c. (effects on 9 d.p.c. unknown) and this Bzrp ligand does not rescue fetuses from malformations induced with either 2CdA or MeHg; effects of Ro5-4864 on EtOH-induced craniofacial malformations is unknown for either sensitive (C57BL/6J) or insensitive (C57BL/6N) strains. The 4.0 mg/kg dose of Bzrp ligands is consistent with pharmacological activity in several studies. Pregnant mice were exposed to these agents on 8 d.p.c. (2CdA, EtOH) or 9 d.p.c. (MeHg). The test dose of 2.5 mg/kg 2CdA was modeled for a 5% increased risk of microphthalmia in term fetuses. Full remediation with PK11195 anticipated. The test dose of 5.0 mg/kg MeHg gives an estimated 20% increased risk of microphthalmia-microcephaly (encephalopathy) in term fetuses. Partial remediation with PK11195 is anticipated to <10% malformations. Again the effects of PK11195 on EtOH teratogenicity is not yet known. The sampling time was chosen as the time of p53 protein induction (3.0h to 4.5h post-treatment). Whereas co-treatment with PK11195 suppresses embryonic p53 protein induction Ro5-4864 does not block this reaction. All measurements were on RNA from the embryonic headfold (8 d.p.c.) or prosencephalon (9 d.p.c.). Keywords = peripheral benzodiazepine receptor Keywords = Bzrp ligands Keywords = PK11195 Keywords = Ro5-4864 Keywords = embryo Keywords = p53 protein induction Keywords: ordered
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