Integrated multi-omics analysis reveals the underlying molecular mechanism for developmental neurotoxicity of perfluorooctanesulfonic acid in zebrafish

Lee, Hyojin; Sung, Eun Ji; Seo, Seung‐Woo; Min, Eun Ki; Lee, Ji-Young; Shim, Ilseob; Kim, Pilje; Kim, Tae‐Young; Lee, Sangkyu; Kim, Ki-Tae

doi:10.1016/j.envint.2021.106802

Cited by 42 publications

(14 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition to apparent targeting of liver (based on ROS production and metabolite profiles), increased ROS production was observed in the brain region of PFOS-exposed embryos, consistent with previous studies that have suggested neurotoxicity of PFAS including PFOS in the zebrafish embryo model (Gaballah et al, 2020;Gebreab et al, 2020;Lee et al, 2021). Further supporting targeting of the central nervous system (CNS), a significant increase in the neuron-specific metabolite, NAA was observed in 72-hpf embryos exposed to PFOS, suggesting impacts on neuronal and/or glial function at this later stage of development.…”

Section: Integrated Cellular Model Of Pfos Toxicitysupporting

confidence: 89%

An Integrated Metabolomics‐Based Model, and Identification of Potential Biomarkers, of Perfluorooctane Sulfonic Acid Toxicity in Zebrafish Embryos

Annunziato,

Bashirova,

Eeza

et al. 2024

Enviro Toxic and Chemistry

View full text Add to dashboard Cite

Known for their high stability and surfactant properties, per‐ and polyfluoroalkyl substances (PFAS) have been widely used in a range of manufactured products. Despite being largely phased out due to concerns regarding their persistence, bioaccumulation, and toxicity, legacy PFAS such as perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid continue to persist at high levels in the environment, posing risks to aquatic organisms. We used high‐resolution magic angle spinning nuclear magnetic resonance spectroscopy in intact zebrafish (Danio rerio) embryos to investigate the metabolic pathways altered by PFOS both before and after hatching (i.e., 24 and 72 h post fertilization [hpf], respectively). Assessment of embryotoxicity found embryo lethality in the parts‐per‐million range with no significant difference in mortality between the 24‐ and 72‐hpf exposure groups. Metabolic profiling revealed mostly consistent changes between the two exposure groups, with altered metabolites generally associated with oxidative stress, lipid metabolism, energy production, and mitochondrial function, as well as specific targeting of the liver and central nervous system as key systems. These metabolic changes were further supported by analyses of tissue‐specific production of reactive oxygen species, as well as nontargeted mass spectrometric lipid profiling. Our findings suggest that PFOS‐induced metabolic changes in zebrafish embryos may be mediated through previously described interactions with regulatory and transcription factors leading to disruption of mitochondrial function and energy metabolism. The present study proposes a systems‐level model of PFOS toxicity in early life stages of zebrafish, and also identifies potential biomarkers of effect and exposure for improved environmental biomonitoring. Environ Toxicol Chem 2024;00:1–19. © 2024 SETAC

show abstract

Section: Integrated Cellular Model Of Pfos Toxicitysupporting

confidence: 89%

An Integrated Metabolomics‐Based Model, and Identification of Potential Biomarkers, of Perfluorooctane Sulfonic Acid Toxicity in Zebrafish Embryos

Annunziato,

Bashirova,

Eeza

et al. 2024

Enviro Toxic and Chemistry

View full text Add to dashboard Cite

show abstract

“…The evidence from transcriptome and DNA methylome also figured out a changing profile of neurotransmission and phototransduction in zebrafish larvae. Hence, the contents of neurotransmitters as well as light–dark stimulated locomotor behavior were used as endpoints to examine the potential neurodevelopmental toxicity. , …”

Section: Resultsmentioning

confidence: 99%

“…Hence, the contents of neurotransmitters as well as light−dark stimulated locomotor behavior were used as endpoints to examine the potential neurodevelopmental toxicity. 59,60 In F1 larvae, the contents of γ-aminobutyric (GABA), acetylcholine (ACh), choline, dopamine (DA), norepinephrine (NE), serotonin (5-HT), and epinephrine (Epi), and 5hydroxyindoleacetic acid (5-HIAA) were significantly elevated (Figure 5A). Meanwhile, the hyperactivity of larvae was observed during both light and dark cycles (Figure 5B,D).…”

Section: Dbdpe Induced Multi-and Transgenerational Glycolipid and Ene...mentioning

confidence: 99%

Multi- and Transgenerational Developmental Impairments Are Induced by Decabromodiphenyl Ethane (DBDPE) in Zebrafish Larvae

Sun

Zhou

Zhu

et al. 2023

Environ. Sci. Technol.

View full text Add to dashboard Cite

A novel brominated flame retardant decabromodiphenyl ethane (DBDPE) has become a ubiquitous emerging pollutant; hence, the knowledge of its long-term toxic effects and underlying mechanism would be critical for further health risk assessment. In the present study, the multi-and transgenerational toxicity of DBDPE was investigated in zebrafish upon a life cycle exposure at environmentally relevant concentrations. The significantly increased malformation rate and declined survival rate specifically occurred in unexposed F2 larvae suggested transgenerational development toxicity by DBDPE. The changing profiles revealed by transcriptome and DNA methylome confirmed an increased susceptibility in F2 larvae and figured out potential disruptions of glycolipid metabolism, mitochondrial energy metabolism, and neurodevelopment. The changes of biochemical indicators such as ATP production confirmed a disturbance in the energy metabolism, whereas the alterations of neurotransmitter contents and light−dark stimulated behavior provided further evidence for multi-and transgenerational neurotoxicity in zebrafish. Our findings also highlighted the necessity for considering the long-term impacts when evaluating the health of wild animals as well as human beings by emerging pollutants.

show abstract

“…17 With the continuous development of molecular biotechnology, omics research can effectively uncover the underlying molecular mechanism of action and the targets of environmental toxicants in the aquatic animal model. 18,19 The integrated omics analysis has been adopted by researchers to elucidate the unique pathways and multifaceted mechanisms. For example, combined transcriptomics and metabolomics clarified the toxic effects in grass carp under anesthetic stress.…”

Section: Introductionmentioning

confidence: 99%

Effect of chronic deltamethrin exposure on brain transcriptome and metabolome of juvenile crucian carp

Wu,

Gao,

Xie

et al. 2023

Environmental Toxicology

View full text Add to dashboard Cite

Deltamethrin (Del), a widely administered pyrethroid insecticide, has been established as a common contaminant of the freshwater environment and detected in many freshwater ecosystems. In this study, we investigated the changes in brain transcriptome and metabolome of crucian carp after exposure to 0.6 μg/L Del for 28 days. Elevated MDA levels and inhibition of SOD activity indicate damage to the antioxidant system. Moreover, a total of 70 differential metabolites (DMs) were identified using the liquid chromatography‐mass spectrometry, including 32 upregulated and 38 downregulated DMs in the Del‐exposed group. The DMs associated with chronic Del exposure were enriched in steroid hormone biosynthesis, fatty acid metabolism, and glycerophospholipid metabolism for prostaglandin G2, 5‐oxoeicosatetraenoic acid, progesterone, androsterone, etiocholanolone, and hydrocortisone. Transcriptomics analysis revealed that chronic Del exposure caused lipid metabolism disorder, endocrine disruption, and proinflammatory immune response by upregulating the pla2g4, cox2, log5, ptgis, lcn, and cbr expression. Importantly, the integrative analysis of transcriptomics and metabolomics indicated that the arachidonic acid metabolism pathway and steroid hormone biosynthesis were decisive processes in the brain tissue of crucian carp after Del exposure. Furthermore, Del exposure perturbed the tight junction, HIF‐1 signaling pathway, and thyroid hormone signaling pathway. Overall, transcriptome and metabolome data of our study offer a new insight to assess the risk of chronic Del exposure in fish brains.

show abstract

Integrated multi-omics analysis reveals the underlying molecular mechanism for developmental neurotoxicity of perfluorooctanesulfonic acid in zebrafish

Cited by 42 publications

References 55 publications

An Integrated Metabolomics‐Based Model, and Identification of Potential Biomarkers, of Perfluorooctane Sulfonic Acid Toxicity in Zebrafish Embryos

An Integrated Metabolomics‐Based Model, and Identification of Potential Biomarkers, of Perfluorooctane Sulfonic Acid Toxicity in Zebrafish Embryos

Multi- and Transgenerational Developmental Impairments Are Induced by Decabromodiphenyl Ethane (DBDPE) in Zebrafish Larvae

Effect of chronic deltamethrin exposure on brain transcriptome and metabolome of juvenile crucian carp

Contact Info

Product

Resources

About