Maternal administration of nanomaterials elicits hemoglobin upregulation in the neonatal brain of non-human primates

Mitsunaga, Fusako; Umezawa, Masakazu; Takeda, Ken; Nakamura, Shin

doi:10.2131/jts.41.265

Cited by 6 publications

(6 citation statements)

References 36 publications

(39 reference statements)

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“…Alternations in gene expression in the placenta have further confirmed that upregulated pathways are related to hypoxia in PE [51]. The expression of HBB was shown to be altered because of its responses to oxidative or nitrosative stress, and/or hypoxia, in the rhesus macaques fetal/neonatal brain [52]. Owing to its ability to reversibly bind O 2 and other gaseous ligands in erythrocytes, HBB could also be used as a therapeutic target to improve the clinical manifestations caused by hypoxia.…”

Section: Discussionmentioning

confidence: 84%

Identification of Differentially Expressed Genes and Signaling Pathways in Placenta Tissue of Early-Onset and Late-Onset Pre-Eclamptic Pregnancies by Integrated Bioinformatics Analysis

et al. 2020

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Departmental sources Background:Pre-eclampsia (PE) can be divided into 2 sub-groups: early-onset and late-onset PE. Although these sub-groups show overlapping molecular and cellular mechanisms and similar clinical manifestations, they are regarded as 2 different phenotypes with heterogeneous manifestations. The pathophysiological mechanisms underlying early-onset and late-onset PE still remain unclear. Therefore, the present study aimed to identify the key genes and pathways related to early-onset and late-onset PE, and to investigate the molecular mechanisms that are involved in gene regulation. Material/Methods:Our analysis involved the Gene Expression Series (GSE) 74341 and GSE22526 from the National Center of Biotechnology Information (NCBI) Gene Expression Omnibus Database. These 2 microarray datasets included 15 patients with early-onset PE and 15 patients with late-onset PE. Results:Our analyses identified 15 differentially expressed genes (DEGs), including CGA, EGR1, HBB, HBA2, LEP, and LHB. Gene Ontology (GO) functional annotation showed that the biological functions of these DEGs were mainly associated with steroid biosynthetic, oxidative stress, angiogenesis, and sex differentiation. Signaling pathway analyses showed that these DEGs were mainly involved in the prolactin signaling pathway, hormone metabolism, the AMPK signaling pathway, and the FoxO signaling pathway. Protein-protein interaction (PPI) network analysis identified 4 genes with the highest degree of interaction. The hub genes for this selection of DEGS were EGR1, LEP, and HBB. Conclusions:Integrated bioinformatic analyses provide us with a new approach to further understand the pathophysiology and molecular mechanisms underlying early-onset and late-onset PE. The DEGs identified in this study represent potential biomarkers for the early diagnosis of PE and may provide significant options the treatment of these 2 subtypes of PE.

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Section: Discussionmentioning

confidence: 84%

Identification of Differentially Expressed Genes and Signaling Pathways in Placenta Tissue of Early-Onset and Late-Onset Pre-Eclamptic Pregnancies by Integrated Bioinformatics Analysis

et al. 2020

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“…The authors also state that hemoglobin upregulation may be a consequence of oxidative or inflammatory stress, or hypoxia; therefore, at least initially, the increased hemoglobin is a protective mechanism. The authors state that higher levels of hemoglobin are reportedly neurotoxic; however, the level of increase necessary to cause neurotoxicity is not stated (Mitsunaga et al 2016).…”

Section: Developmental Effectsmentioning

confidence: 99%

Evaluating the evidence on genotoxicity and reproductive toxicity of carbon black: a critical review

Chaudhuri

Fruijtier-Pölloth²,

Ngiewih

et al. 2017

Critical Reviews in Toxicology

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Carbon black is produced industrially by the partial combustion or thermal decomposition of gaseous or liquid hydrocarbons under controlled conditions. It is considered a poorly soluble, low toxicity (PSLT) particle. Recently, results from a number of published studies have suggested that carbon black may be directly genotoxic, and that it may also cause reproductive toxicity. Here, we review the evidence from these studies to determine whether carbon black is likely to act as a primary genotoxicant or reproductive toxicant in humans. For the genotoxicity endpoint, the available evidence clearly shows that carbon black does not directly interact with DNA. However, the study results are consistent with the mechanism that, at high enough concentrations, carbon black causes inflammation and oxidative stress in the lung leading to mutations, which is a secondary genotoxic mechanism. For the reproductive toxicity endpoint for carbon black, to date, there are various lung instillation studies and one short-term inhalation study that evaluated a selected number of reproduction endpoints (e.g. gestational and litter parameters) as well as other general endpoints (e.g. gene expression, neurofunction, DNA damage); usually at one time point or using a single dose. It is possible that some of the adverse effects observed in these studies may be the result of non-specific inflammatory effects caused by high exposure doses. An oral gavage study reported no adverse reproductive or developmental effects at the highest dose tested. The overall weight of evidence indicates that carbon black should not be considered a direct genotoxicant or reproductive toxicant.

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“…Umezawa et al (2014) also reported that the degree of the risk on offspring depends on the type of nanoparticles. Furthermore, many other animal studies also reported that exposure to UFPs provokes fetal brain dysfunction (Shimizu et al, 2009;Takeda et al, 2009;Takahashi et al, 2010;Mitsunaga et al, 2016;Onoda et al, 2017). Ambient fine particles contain a large proportion of UFPs; due to their small size, UFPs have high physicochemical reactivity and show unique behaviors in vivo including the following three potential pathways: 1) release of proinflammatory mediators from lung cells, 2) affect autonomic nervous system balance by particle interactions with lung receptors or nerves, and 3) translocation of UFPs and soluble particle components into the systemic circulation.…”

Section: Fine Particles Affect Fetal Healthmentioning

confidence: 95%

“…An integral role of reactive oxygen species (ROS)-dependent pathways has been suggested in systemic pro-inflammatory responses and vascular dysfunction at the molecular level ( Brook et al, 2010 ). Although epidemiological studies on the health effects of UFPs also are needed, exposure assessment for atmospheric UFPs is complex ( Sioutas et al, 2005 ) and emerging evidence on UFPs health effects has mainly led by experimental studies using animals ( Sugamata et al, 2006 ; Shimizu et al, 2009 ; Takeda et al, 2009 ; Takahashi et al, 2010 ; Kubo-Irie et al, 2014 ; Onoda et al, 2014 ; Shimizu et al, 2014 ; El-Sayed et al, 2015 ; Mitsunaga et al, 2016 ; Onoda et al, 2017 ) and cells ( Xia et al, 2004 ; Mo et al, 2009 ; Li et al, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

“…Many studies have suggested that fine particulates air pollution is related to developmental and reproductive ( Gilboa et al, 2005 ; Shimizu et al, 2009 ; Takeda et al, 2009 ; Takahashi et al, 2010 ; Dadvand et al, 2013 ; Volk et al, 2013 ; Yokota et al, 2013 ; Onoda et al, 2014 ; Kubo-Irie et al, 2014 ; Symanski et al, 2014 ; El-Sayed et al, 2015 ; Tachibana et al, 2015 ; DeFranco et al, 2016 ; Mitsunaga et al, 2016 ; Yokota et al, 2016 ; Carré et al, 2017 ; Chen et al, 2017 ; Martens et al, 2017 ; Onoda et al, 2017 ). The impact of air pollutants on the next generation is of great concern, and preventive measures are required.…”

Section: Introductionmentioning

confidence: 99%

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Potential of NRF2 Pathway in Preventing Developmental and Reproductive Toxicity of Fine Particles

Takeda

Yamamoto

et al. 2021

Front. Toxicol.

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Air pollution is associated with significant adverse health effects. Recent studies support the idea that inhalation of fine particles can instigate extrapulmonary effects on the cardiovascular system through several pathways. The systemic transfer of ultrafine particles (UFPs) or soluble particle components (organic compounds and metals) is of particular concern. An integral role of reactive oxygen species (ROS)-dependent pathways has been suggested in systemic inflammatory responses and vascular dysfunction at the molecular level. Accumulating lines of evidence suggest that fine particles affect fetal development, giving rise to low birth weight and a reduction in fetal growth, and also affect the immune, cardiovascular, and central nervous systems. Oxidative stress plays an important role in fine particles toxicity; pre-treatment with antioxidants partially suppresses the developmental toxicity of fine particles. On the other hand, Nuclear factor erythroid-derived 2-like 2 (Nfe2l2), also known as NRF2, is a transcription factor essential for inducible and/or constitutive expression of phase II and antioxidant enzymes. Studies using Nrf2-knockout mice revealed that NRF2 dysfunction is intimately involved in the pathogenesis of various human diseases. Multiple single nucleotide polymorphisms (SNPs) have been detected in human NRF2 locus. An NRF2 gene SNP (−617C > A; rs6721961), located in the upstream promoter region, affects the transcriptional level of NRF2 and thereby the protein level and downstream gene expression. It has been reported that the SNP-617 is associated with various diseases. The onset and exacerbation of the diseases are regulated by genetic predisposition and environmental factors; some people live in the air-polluted environment but are not affected and remain healthy, suggesting the presence of individual differences in the susceptibility to air pollutants. NRF2 polymorphisms may also be associated with the fetal effects of fine particles exposure. Screening high-risk pregnant women genetically susceptible to oxidative stress and prevention by antioxidant interventions to protect fetal development in air-polluted areas should be considered. This article reviews the recent advances in our understanding of the fetal health effects of fine particles and describes potential chemoprevention via the NRF2 pathway to prevent the developmental and reproductive toxicity of fine particles.

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Maternal administration of nanomaterials elicits hemoglobin upregulation in the neonatal brain of non-human primates

Cited by 6 publications

References 36 publications

Identification of Differentially Expressed Genes and Signaling Pathways in Placenta Tissue of Early-Onset and Late-Onset Pre-Eclamptic Pregnancies by Integrated Bioinformatics Analysis

Identification of Differentially Expressed Genes and Signaling Pathways in Placenta Tissue of Early-Onset and Late-Onset Pre-Eclamptic Pregnancies by Integrated Bioinformatics Analysis

Evaluating the evidence on genotoxicity and reproductive toxicity of carbon black: a critical review

Potential of NRF2 Pathway in Preventing Developmental and Reproductive Toxicity of Fine Particles

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