Dataset Information

Treating the placenta with nanoparticles to prevent altered placental secretion and fetal development in response to hypoxia [Fetal Plasma]

ABSTRACT: Hypoxia-related pregnancy complications increase the risk of disease in the child in later life. No prevention is available. Previously we noted that a trophoblast barrier, an in vitro model of the placenta, reacted to oxidative stress by secreting factors that damage neighbouring cells. Application of mitochondrion-targeted antioxidant MitoQ prevented this. Here we tested the effects of MitoQ-bound nanoparticles on trophoblast barriers and in a rat model of gestational hypoxia.A single dose of MitoQ-nanoparticles, administered maternally before a hypoxic episode, reduced oxidative stress in the placental barrier without reaching the fetus and prevented changes to birthweight. MitoQ-nanoparticles further suppressed damaging signalling from the placental barriers. Altered signalling molecules in the fetal plasma and in conditioned media from rat placenta included changes to proteins with relevance to cardiovascular disease. We suggest as a future possibility, treatment of the placenta to prevent disease in the offspring in later life.

OTHER RELATED OMICS DATASETS IN: GSE86410PRJNA341488PRJNA341704PRJNA341706

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Blood Plasma

SUBMITTER: Hannah Scott

LAB HEAD: Patrick Case

PROVIDER: PXD004955 | Pride | 2017-08-22

REPOSITORIES: Pride

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Publications

Treating the placenta to prevent adverse effects of gestational hypoxia on fetal brain development.

Phillips Tom J TJ Scott Hannah H Menassa David A DA Bignell Ashleigh L AL Sood Aman A Morton Jude S JS Akagi Takami T Azuma Koki K Rogers Mark F MF Gilmore Catherine E CE Inman Gareth J GJ Grant Simon S Chung Yealin Y Aljunaidy Mais M MM Cooke Christy-Lynn CL Steinkraus Bruno R BR Pocklington Andrew A Logan Angela A Collett Gavin P GP Kemp Helena H Holmans Peter A PA Murphy Michael P MP Fulga Tudor A TA Coney Andrew M AM Akashi Mitsuru M Davidge Sandra T ST Case C Patrick CP

Scientific reports 20170822 1

Some neuropsychiatric disease, including schizophrenia, may originate during prenatal development, following periods of gestational hypoxia and placental oxidative stress. Here we investigated if gestational hypoxia promotes damaging secretions from the placenta that affect fetal development and whether a mitochondria-targeted antioxidant MitoQ might prevent this. Gestational hypoxia caused low birth-weight and changes in young adult offspring brain, mimicking those in human neuropsychiatric dis ...[more]

PMID: 28831049

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Project description:Pancreatic cancer is a complex disease with a desmoplastic stroma, extreme hypoxia, and inherent resistance to therapy. Understanding the signaling and adaptive response of such an aggressive cancer is key to making advances in therapeutic efficacy and understanding disease progression. Redox factor-1 (Ref-1), a redox signaling protein, regulates the DNA binding activity of several transcription factors, including HIF-1. The conversion of HIF-1 from an oxidized to reduced state leads to enhancement of its DNA binding. In our previously published work, knockdown of Ref-1 under normoxia resulted in altered gene expression patterns on pathways including EIF2, protein kinase A, and mTOR. In this study, single cell RNA sequencing (scRNA-seq) and proteomics were used to explore the effects of Ref-1 on metabolic pathways under hypoxia.Results: We also integrated the scRNA data analysis with the proteomic analysis and found that the differentially expressed genes and pathways identified from the scRNA-seq data are highly consistent to the significant proteins observed in the proteomics data, especially for the upregulated cell cycle and transcription pathways and downregulated metabolic, apoptosis and signaling pathways under hypoxia. Conclusion: The scRNA-seq and proteomics data consistently demonstrated down-regulated central metabolism pathways in APE1/Ref-1 knockdown vs scrambled control under both normoxia and hypoxia conditions. Experimental Methods: scRNA-seq comparing pancreatic cancer cells expressing less than 20% of the Ref-1 protein was analyzed using left truncated mixture Gaussian model. Matched samples were also collected for bulk proteomic analysis of the four conditions. scRNA-seq data was validated using proteomics and qRT-PCR. Ref-1’s role in mitochondrial function was confirmed using mitochondrial function assays and qRT-PCR. Results: We also integrated the scRNA data analysis with the proteomic analysis and found that the differentially expressed genes and pathways identified from the scRNA-seq data are highly consistent to the significant proteins observed in the proteomics data, especially for the upregulated cell cycle and transcription pathways and downregulated metabolic, apoptosis and signaling pathways under hypoxia. Conclusion: The scRNA-seq and proteomics data consistently demonstrated down-regulated central metabolism pathways in APE1/Ref-1 knockdown vs scrambled control under both normoxia and hypoxia conditions.

			Action	DRS
	FetalPlasma_Result.mzid	Mzid
	FetalPlasma_Search.msf	Msf
	Fraction_1.mzML	Mzml
	Fraction_1.raw	Raw
	Fraction_10.mzML	Mzml