Perinatal exposure to FireMaster® 550 (FM550), brominated or organophosphate flame retardants produces sex and compound specific effects on adult Wistar rat socioemotional behavior

Witchey, Shannah K.; Samara, Loujain Al; Horman, Brian; Stapleton, Heather M.; Patisaul, Heather B.

doi:10.1016/j.yhbeh.2020.104853

Cited by 27 publications

(30 citation statements)

References 110 publications

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“…Therefore, it appears that PBDE effects on social behavior may be congener- and/or dose-specific. Our findings are supported by perinatal exposure studies using another flame retardant mixture Firemaster 550 (6.6 mg/kg/day) and its BFR and organophosphate components (3.3 mg/kg/d), which produce deficits in social recognition after 24 h retention in a sex- and exposure-specific manner in rats (Witchey et al 2020 ). Perinatal exposure to Firemaster 550 also produces abnormal partner preference in female prairie voles (1 mg/kg; Gillera et al 2020 ).…”

Section: Discussionsupporting

confidence: 82%

“…EDC chemicals include phytoestrogens like genestein, chlorpyrifos, diethystilbestrol, bisphenol A (BPA), organophosphate pesticides and organohalogens like PCBs, PBDEs and Firemaster 500 (Patisaul 2017 ). For example, we and others have shown that some of these EDCs such as Firemaster 550 (Gillera et al 2021 ), PCBs such as A122 (Reilly et al 2021 ) and A1254 (Coburn et al 2005 ); (Coburn et al 2007 ) and BPA (Witchey et al 2020 ) have endocrine disruptive effects on the oxytocin and/or vasopressin systems and, in some cases, these are concomitant with their effects on social behavior (Witchey et al 2020 ); (Gillera et al 2020 ); (Hernandez Scudder et al 2020 ); (Reilly et al 2021 ).…”

Section: Discussionmentioning

confidence: 92%

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Persistent autism-relevant behavioral phenotype and social neuropeptide alterations in female mice offspring induced by maternal transfer of PBDE congeners in the commercial mixture DE-71

et al. 2021

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Polybrominated diphenyl ethers (PBDEs) are ubiquitous persistent organic pollutants (POPs) that are known neuroendocrine disrupting chemicals with adverse neurodevelopmental effects. PBDEs may act as risk factors for autism spectrum disorders (ASD), characterized by abnormal psychosocial functioning, although direct evidence is currently lacking. Using a translational exposure model, we tested the hypothesis that maternal transfer of a commercial mixture of PBDEs, DE-71, produces ASD-relevant behavioral and neurochemical deficits in female offspring. C57Bl6/N mouse dams (F0) were exposed to DE-71 via oral administration of 0 (VEH/CON), 0.1 (L-DE-71) or 0.4 (H-DE-71) mg/kg bw/d from 3 wk prior to gestation through end of lactation. Mass spectrometry analysis indicated in utero and lactational transfer of PBDEs (in ppb) to F1 female offspring brain tissue at postnatal day (PND) 15 which was reduced by PND 110. Neurobehavioral testing of social novelty preference (SNP) and social recognition memory (SRM) revealed that adult L-DE-71 F1 offspring display deficient short- and long-term SRM, in the absence of reduced sociability, and increased repetitive behavior. These effects were concomitant with reduced olfactory discrimination of social odors. Additionally, L-DE-71 exposure also altered short-term novel object recognition memory but not anxiety or depressive-like behavior. Moreover, F1 L-DE-71 displayed downregulated mRNA transcripts for oxytocin (Oxt) in the bed nucleus of the stria terminalis (BNST) and supraoptic nucleus, and vasopressin (Avp) in the BNST and upregulated Avp1ar in BNST, and Oxtr in the paraventricular nucleus. Our work demonstrates that developmental PBDE exposure produces ASD-relevant neurochemical, olfactory processing and behavioral phenotypes that may result from early neurodevelopmental reprogramming within central social and memory networks.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 92%

Persistent autism-relevant behavioral phenotype and social neuropeptide alterations in female mice offspring induced by maternal transfer of PBDE congeners in the commercial mixture DE-71

et al. 2021

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“…Our findings are also supported by perinatal exposure studies using other BFRs such as Firemaster 550 (6.6 mg/kg/day) and its BFR and organophosphate components alone (3.3 mg/kg/d), which produce deficits in social recognition after 24 h retention in a sex and exposure-specific manner in rats 108 . Perinatal exposure to Firemaster 550 also produces abnormal partner preference in female prairie voles (1 mg/kg) 109 .…”

Section: Discussionsupporting

confidence: 81%

Persistent autism-relevant phenotype produced by in utero and lactational exposure of female mice to the commercial PBDE mixture, DE-71

Kozlova

Valdez

Denys

et al. 2021

Preprint

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Polybrominated diphenyl ethers (PBDEs) are ubiquitous persistent organic pollutants (POPs) that are known neuroendocrine disrupting chemicals with adverse neurodevelopmental effects. PBDEs may act as risk factors for autism spectrum disorders (ASD), characterized by abnormal psychosocial functioning, although direct evidence is currently lacking. Using a translational exposure model, we tested the hypothesis that maternal transfer of a commercial mixture of PBDEs, DE-71, produces ASD-relevant behavioral and neurochemical deficits in female offspring. C57Bl6/N mouse dams (F0) were exposed to DE-71 via oral administration of 0 (VEH/CON), 0.1 (L-DE-71) or 0.4 (H-DE-71) mg/kg bw/d from 3 wk prior to gestation through lactation. Mass spectrometry analysis indicated in utero and lactational transfer of PBDEs (ppb) to F1 female offspring brain tissue at postnatal day (PND) 15 which was reduced by PND 110. Neurobehavioral testing of social novelty preference (SNP) and social recognition memory (SRM) revealed that adult L-DE-71 F1 offspring display altered short- and long-term SRM, in the absence of reduced sociability, and increased repetitive behavior. These effects were concomitant with reduced olfactory discrimination of social odors. Additionally, L-DE-71 exposure also altered short-term novel object recognition memory but not anxiety or depressive-like behavior. Moreover, F1 L-DE-71 displayed downregulated mRNA transcripts for oxytocin (Oxt) in the bed nucleus of the stria terminalis (BNST) and supraoptic nucleus, vasopressin (Avp) in the BNST and upregulated Avp1ar in BNST, and Oxtr in the paraventricular nucleus. Our work demonstrates that developmental PBDE exposure produces ASD-relevant neurochemical, olfactory processing and behavioral phenotypes that may result from early neurodevelopmental reprogramming within central social and memory networks.

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“…FM 550 components or metabolites are routinely detected in human tissues including breast milk, blood, hair, fingernails and urine [ 46 , 47 , 48 ] with children having higher levels than adults [ 49 , 50 , 51 , 52 ]. Compounding evidence from us and others shows that FM 550 can adversely impact socio-emotional behavior and neurodevelopment [ 33 , 35 , 53 , 54 , 55 , 56 , 57 , 58 , 59 ], and epidemiological studies have linked maternal exposure to FM 550 or its components with impaired cognitive and behavioral performance in children [ 60 , 61 ]. Finally, our lab has also repeatedly shown in rodents that developmental exposure to FM 550 or its components alters, in a sexually dimorphic manner, anxiety-like [ 55 , 56 , 59 ] and socio-emotional behaviors, including pair-bonding in the socially monogamous species, the prairie vole [ 57 , 58 ].…”

Section: Introductionmentioning

confidence: 99%

“…Dams were not dosed by individual weight, but rather by the average colony weight of 50 g during pregnancy, producing exposures of approximately 20 mg/kg BW. Dose selection was based on our prior behavioral studies in rats and voles [ 56 , 57 ], and because it is well below the presumed NOAEL of 50 mg/kg/bw per day for the BFR combination in FM 550 [ 79 ]. To generate the PD groups, sires were removed the day after birth.…”

Section: Introductionmentioning

confidence: 99%

Individual and Combined Effects of Paternal Deprivation and Developmental Exposure to Firemaster 550 on Socio-Emotional Behavior in Prairie Voles

Gillera

Marinello

Nelson

et al. 2022

Toxics

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The prevalence of neurodevelopmental disorders (NDDs) is rapidly rising, suggesting a confluence of environmental factors that are likely contributing, including developmental exposure to environmental contaminants. Unfortunately, chemical exposures and social stressors frequently occur simultaneously in many communities, yet very few studies have sought to establish the combined effects on neurodevelopment or behavior. Social deficits are common to many NDDs, and we and others have shown that exposure to the chemical flame retardant mixture, Firemaster 550 (FM 550), or paternal deprivation impairs social behavior and neural function. Here, we used a spontaneously prosocial animal model, the prairie vole (Microtus ochrogaster), to explore the effects of perinatal chemical (FM 550) exposure alone or in combination with an early life stressor (paternal absence) on prosocial behavior. Dams were exposed to vehicle (sesame oil) or 1000 µg FM 550 orally via food treats from conception through weaning and the paternal absence groups were generated by removing the sires the day after birth. Adult offspring of both sexes were then subjected to open-field, sociability, and a partner preference test. Paternal deprivation (PD)-related effects included increased anxiety, decreased sociability, and impaired pair-bonding in both sexes. FM 550 effects include heightened anxiety and partner preference in females but reduced partner preference in males. The combination of FM 550 exposure and PD did not exacerbate any behaviors in either sex except for distance traveled by females in the partner preference test and, to a lesser extent, time spent with, and the number of visits to the non-social stimulus by males in the sociability test. FM 550 ameliorated the impacts of parental deprivation on partner preference behaviors in both sexes. This study is significant because it provides evidence that chemical and social stressors can have unique behavioral effects that differ by sex but may not produce worse outcomes in combination.

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Perinatal exposure to FireMaster® 550 (FM550), brominated or organophosphate flame retardants produces sex and compound specific effects on adult Wistar rat socioemotional behavior

Cited by 27 publications

References 110 publications

Persistent autism-relevant behavioral phenotype and social neuropeptide alterations in female mice offspring induced by maternal transfer of PBDE congeners in the commercial mixture DE-71

Persistent autism-relevant behavioral phenotype and social neuropeptide alterations in female mice offspring induced by maternal transfer of PBDE congeners in the commercial mixture DE-71

Persistent autism-relevant phenotype produced by in utero and lactational exposure of female mice to the commercial PBDE mixture, DE-71

Individual and Combined Effects of Paternal Deprivation and Developmental Exposure to Firemaster 550 on Socio-Emotional Behavior in Prairie Voles

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