A multi-omics approach reveals molecular mechanisms by which phthalates induce cardiac defects in zebrafish (Danio rerio)

Mu, Xiyan; Chen, Xiaofeng; Liu, Jia; Yuan, Lilai; Wang, Donghui; Qian, Le; Qian, Yu; Shen, Guoan; Huang, Ying; Li, Xuxing; Li, Yingren; Lin, Xiangming

doi:10.1016/j.envpol.2019.113876

Cited by 38 publications

(19 citation statements)

References 63 publications

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“…Studies report that DEHP could impose cardiovascular toxicity to zebrafish embryos. Treatment with 250 µg/L DEHP induced intense apoptotic signals in the heart region in zebrafish embryos at 72 hpf relative to the control [ 52 ]. On the other hand, DEHP was reported to induce pericardial edema in zebrafish embryos [ 41 , 44 , 52 ].…”

Section: Acute Effects Induced By Acute Exposurementioning

confidence: 99%

“…Treatment with 250 µg/L DEHP induced intense apoptotic signals in the heart region in zebrafish embryos at 72 hpf relative to the control [ 52 ]. On the other hand, DEHP was reported to induce pericardial edema in zebrafish embryos [ 41 , 44 , 52 ]. Pericardial edema was observed at 72 or 96 hpf after treatment with DEHP in the µg/L range [ 44 , 52 ].…”

Section: Acute Effects Induced By Acute Exposurementioning

confidence: 99%

“…On the other hand, DEHP was reported to induce pericardial edema in zebrafish embryos [ 41 , 44 , 52 ]. Pericardial edema was observed at 72 or 96 hpf after treatment with DEHP in the µg/L range [ 44 , 52 ]. Exposure to a higher DEHP concentration (10 mg/L) from 72 to 168 hpf also led to the same effect [ 41 ].…”

Section: Acute Effects Induced By Acute Exposurementioning

confidence: 99%

“…On the other hand, multi-omics approaches were also employed to investigate the mechanisms of DEHP-induced developmental toxicities [ 48 , 52 ]. Omics approaches in biology, including genomics, epigenomics, transcriptomics, proteomics, lipidomics and metabolomics, can reveal alterations in different domains upon toxicant exposures and provide insights into possible mechanisms as well as potential toxic effects and diseases [ 54 ].…”

Section: Acute Effects Induced By Acute Exposurementioning

confidence: 99%

“…Based on these findings, the authors inferred that DEHP-induced immune response might be a result of disruption of lipid homeostasis [ 48 ]. In a separate study, Mu et al further investigated possible developmental pathways upon exposures to 50 µg/L of DEHP via transcriptomic and DNA methylation profile analysis, particularly the genes involved in heart development [ 52 ]. From transcriptomic analyses, among 32,477 genes in the reference genome of zebrafish, the research group reported that 371 transcripts (234 up-regulated and 137 down-regulated) were significantly altered in embryos after their exposure to 50 µg/L DEHP, followed by the gene ontology analysis.…”

Section: Acute Effects Induced By Acute Exposurementioning

confidence: 99%

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Review on Toxic Effects of Di(2-ethylhexyl) Phthalate on Zebrafish Embryos

Kwan

Roy

2021

Toxics

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Di(2-ethylhexyl) phthalate (DEHP) is widely used as a plasticizer in consumer products. People are continuously exposed to DEHP through ingestion, inhalation and dermal absorption. From epidemiological studies, DEHP has been shown to associate with various adverse health effects, such as reproductive abnormalities and metabolic diseases. Health concerns have been raised regarding DEHP exposures; therefore, relevant risk assessment has become necessary through toxicological testing of DEHP. In the past 10 years, an increasing number of DEHP toxicity studies have been using zebrafish embryos as an in vivo model due to their high fecundity, rapid embryonic development as well as optical transparency, which have now been established as an alternative of the more conventional rodent model. The aim of the present paper is to review the effects of acute (from embryo stage to ≤1 week) and chronic (from embryo stage to >1 week) DEHP exposures on zebrafish, which start from the embryonic stage, and to analyze acute and potential long-term effects induced by acute exposure and effects induced by chronic exposure of DEHP upon subjecting to exposures, starting from the embryonic stage to different developmental stages, with a view to facilitate risk assessments on DEHP exposures.

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Section: Acute Effects Induced By Acute Exposurementioning

confidence: 99%

Section: Acute Effects Induced By Acute Exposurementioning

confidence: 99%

Section: Acute Effects Induced By Acute Exposurementioning

confidence: 99%

Section: Acute Effects Induced By Acute Exposurementioning

confidence: 99%

Section: Acute Effects Induced By Acute Exposurementioning

confidence: 99%

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Review on Toxic Effects of Di(2-ethylhexyl) Phthalate on Zebrafish Embryos

Kwan

Roy

2021

Toxics

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Environmental Signals

Porter

2024

Advances in Experimental Medicine and Biology

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Granulocyte-colony stimulating factor ameliorates di-ethylhexyl phthalate-induced cardiac muscle injury via stem cells recruitment, Desmin protein regulation, antifibrotic and antiapoptotic mechanisms

et al. 2023

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Phthalates are common plasticizers present in medical-grade plastics and other everyday products. Di-ethylhexyl phthalate (DEHP) has been noted as a causative risk factor for the initiation and augmentation of cardiovascular functional disorders. G-CSF is a glycoprotein found in numerous tissues throughout the body and is currently applied in clinical practice and has been tested in congestive heart failure. We aimed to examine in depth the effect of DEHP on the histological and biochemical structure of the cardiac muscle in adult male albino rats and the mechanisms underlying the possible ameliorative effect of G-CSF. Forty-eight adult male albino rats were divided into control group, DEHP group, DEHP+ G-CSF group and DEHP-recovery group. We measured serum levels of aspartate aminotransferase (AST), creatine kinase MB isoenzyme (CK-MB) and lactate dehydrogenase (LDH). Left ventricular sections were processed for light and electron microscope examination, and immunohistochemical staining of Desmin, activated Caspase-3 and CD34. DEHP significantly increased enzyme levels, markedly distorted the normal architecture of cardiac muscle fibers, downregulated Desmin protein levels and enhanced fibrosis, and apoptosis. G-CSF treatment significantly decreased the enzyme levels compared to DEHP group. It enhanced CD34 positive stem cells recruitment to injured cardiac muscle, therefore improved the ultrastructural features of most cardiac muscle fibers via anti-fibrotic and anti-apoptotic effects in addition to increased Desmin protein expression levels. The recovery group showed partial improvement due to persistent DEHP effect. In conclusion, administration of G-CSF effectively corrected the histopathological, immunohistochemical and biochemical alterations in the cardiac muscle after DEHP administration by stem cells recruitment, Desmin protein regulation, antifibrotic and antiapoptotic mechanisms.

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A multi-omics approach reveals molecular mechanisms by which phthalates induce cardiac defects in zebrafish (Danio rerio)

Cited by 38 publications

References 63 publications

Review on Toxic Effects of Di(2-ethylhexyl) Phthalate on Zebrafish Embryos

Review on Toxic Effects of Di(2-ethylhexyl) Phthalate on Zebrafish Embryos

Environmental Signals

Granulocyte-colony stimulating factor ameliorates di-ethylhexyl phthalate-induced cardiac muscle injury via stem cells recruitment, Desmin protein regulation, antifibrotic and antiapoptotic mechanisms

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