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Impacts of Gestational FireMaster 550 (FM 550) Exposure on the Neonatal Cortex are Sex Specific and Largely Attributable to the Organophosphate Esters

ABSTRACT: Lipidomic analyses from Agilent 6560 IM-QTOF in both positive and negative mode for brains from rat pups.

INSTRUMENT(S): 6560 Q-TOF LC/MS

ORGANISM(S): Rattus Norvegicus

SUBMITTER: Erin Baker

PROVIDER: MSV000090203 | MassIVE | Wed Aug 24 15:39:00 BST 2022

REPOSITORIES: MassIVE

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Project description:IntroductionFlame retardants (FRs) are common bodily and environmental pollutants, creating concern about their potential toxicity. We and others have found that the commercial mixture FireMaster® 550 (FM 550) or its individual brominated (BFR) and organophosphate ester (OPFR) components are potential developmental neurotoxicants. Using Wistar rats, we previously reported that developmental exposure to FM 550 or its component classes produced sex- and compound-specific effects on adult socioemotional behaviors. The underlying mechanisms driving the behavioral phenotypes are unknown.MethodsTo further mechanistic understanding, here we conducted transcriptomics in parallel with a novel lipidomics approach using cortical tissues from newborn siblings of the rats in the published behavioral study. Inclusion of lipid composition is significant because it is rarely examined in developmental neurotoxicity studies. Pups were gestationally exposed via oral dosing to the dam to FM 550 or the BFR or OPFR components at environmentally relevant doses.ResultsThe neonatal cortex was highly sexually dimorphic in lipid and transcriptome composition, and males were more significantly impacted by FR exposure. Multiple adverse modes of action for the BFRs and OPFRs on neurodevelopment were identified, with the OPFRs being more disruptive than the BFRs via multiple mechanisms including dysregulation of mitochondrial function and disruption of cholinergic and glutamatergic systems. Disrupted mitochondrial function by environmental factors has been linked to a higher risk of autism spectrum disorders and neurodegenerative disorders. Impacted lipid classes included ceramides, sphingomyelins, and triacylglycerides. Robust ceramide upregulation in the OPFR females could suggest a heightened risk of brain metabolic disease.ConclusionsThis study reveals multiple mechanisms by which the components of a common FR mixture are developmentally neurotoxic and that the OPFRs may be the compounds of greatest concern.

Dataset Information

Impacts of Gestational FireMaster 550 (FM 550) Exposure on the Neonatal Cortex are Sex Specific and Largely Attributable to the Organophosphate Esters

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