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Perinatal exposure to organophosphate flame retardants: effects on gene expression, metabolism, feeding and exploratory behavior

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TitleInfo
Title
Perinatal exposure to organophosphate flame retardants: effects on gene expression, metabolism, feeding and exploratory behavior
Name (type = personal)
NamePart (type = family)
Walley
NamePart (type = given)
Sabrina Nicole
NamePart (type = date)
1992-
DisplayForm
Sabrina Nicole Walley
Role
RoleTerm (authority = RULIB)
author
Name (type = personal)
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Roepke
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Troy Adam
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Troy Adam Roepke
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Advisory Committee
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chair
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NamePart (type = family)
Cooper
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Keith
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Keith Cooper
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Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Stapleton
NamePart (type = given)
Phoebe
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Phoebe Stapleton
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = corporate)
NamePart
Rutgers University
Role
RoleTerm (authority = RULIB)
degree grantor
Name (type = corporate)
NamePart
School of Graduate Studies
Role
RoleTerm (authority = RULIB)
school
TypeOfResource
Text
Genre (authority = marcgt)
theses
OriginInfo
DateCreated (encoding = w3cdtf); (qualifier = exact)
2019
DateOther (encoding = w3cdtf); (qualifier = exact); (type = degree)
2019-05
CopyrightDate (encoding = w3cdtf); (qualifier = exact)
2019
Language
LanguageTerm (authority = ISO 639-3:2007); (type = text)
English
Abstract
Following the phase out of polybrominated diphenyl ethers (PBDEs) due to their persistence in the environment and endocrine disrupting properties, organophosphate flame retardants (OPFR) massively increased in production. Because of this persistence, flame retardants (FR) are ubiquitous in the environment and can interact with multiple nuclear receptors, including the estrogen receptors (ERs) and peroxisome proliferating activated receptors (PPARs). While many studies have assessed the effects of developmental exposure to EDCs on energy homeostasis, little is known about FR like OPFRs, individual food intake, metabolic parameters and their effects on metabolic syndrome. Therefore, we investigated maternal OPFR exposure followed by adult high-fat diet (HFD) or low-fat diet (LFD) challenge results in sexually dimorphic differences in behavior, activity and neuropeptides through interactions with steroids and nuclear receptors (experiment 1) and if maternal OPFR exposure with a HFD or LFD challenge results in sexually dimorphic changes in gene expression and higher susceptibility to symptoms
of metabolic syndrome (experiment 2).
In experiment 1, WT C57Bl/6J dams were orally dosed with vehicle (oil) or an OPFR mixture {1mg/kg combination each of tris(1,3-dichloro-2-propyl)phosphate, triphenyl phosphate, and tricresyl phosphate} from gestation day 7 to postnatal day 14. During maternal exposure, anogenital distance (AGD) was measured in pups as an early sign of maternal influences on progeny. Males had a reduced AGD, exhibiting estrogenic or anti-androgenic effects. After weaning, pups were challenged with a high fat (HFD) or low fat diet (LFD). In order to evaluate anxiety- like behavior, we used the elevated plus maze (EPM) and open field test (OFT) and the comprehensive lab animal monitoring system (CLAMS) for general locomotor activity. EPM results found males exhibited more anxiogenic behavior, while females had the same effect in OFT. CLAMS showed a reduction in activity for males. Individual food intake, and meal patterns were quantified with the Biological Data Acquisition System (BioDAQ), which found that OPFR and HFD males ate more during acrophase. Increased energy intake was observed in OPFR HFD female mice. Arcuate (ARC) neuropeptide and hormone receptor expression were measured to assess changes in gene expression, which showed only females had an increase in ARC expression genes. Showing that OPFR, or an interaction of OPFR and diet had a sexually dimorphic effect.
In experiment 2, WT C57Bl/6J dams were orally dosed with vehicle (oil) or an OPFR mixture {1mg/kg combination each of tris(1,3-dichloro-2-propyl)phosphate, triphenyl phosphate, and tricresyl phosphate} from gestation day 7 to postnatal day 14. After weaning, pups were challenged with a high-fat (HFD) or low-fat diet (LFD). As symptoms of metabolic syndrome are not exclusive to obese individuals, we not only analyzed bodyweight and body composition, but other metabolic activity parameters. OPFR altered substrate utilization in both sexes, altered carbon dioxide and oxygen consumption in females following CLAMS use. OPFR altered fasting glucose in females, and glucose and hepatic glucose homeostasis in males. Plasma leptin was reduced in males while liver enzymes and receptors were reduced in both sexes. These data suggest that OPFRs alter ARC and liver homeostatic gene expression and energy balance in a sex-dependent manner.
Subject (authority = local)
Topic
17-╬▓ estradiol (E2)
Subject (authority = RUETD)
Topic
Toxicology
Subject (authority = ETD-LCSH)
Topic
Fire resistant materials -- Toxicology
Subject (authority = ETD-LCSH)
Topic
Environmental health
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_9893
PhysicalDescription
Form (authority = gmd)
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application/pdf
InternetMediaType
text/xml
Extent
1 online resource (x, 133 pages) : illustrations
Note (type = degree)
M.S.
Note (type = bibliography)
Includes bibliographical references
RelatedItem (type = host)
TitleInfo
Title
School of Graduate Studies Electronic Theses and Dissertations
Identifier (type = local)
rucore10001600001
Location
PhysicalLocation (authority = marcorg); (displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Identifier (type = doi)
doi:10.7282/t3-kfwm-3g12
Genre (authority = ExL-Esploro)
ETD graduate
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Rights

RightsDeclaration (ID = rulibRdec0006)
The author owns the copyright to this work.
RightsHolder (type = personal)
Name
FamilyName
Walley
GivenName
Sabrina
MiddleName
Nicole
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2019-04-22 11:41:06
AssociatedEntity
Name
Sabrina Nicole Walley
Role
Copyright holder
Affiliation
Rutgers University. School of Graduate Studies
AssociatedObject
Type
License
Name
Author Agreement License
Detail
I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
RightsEvent
Type
Embargo
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2019-05-31
DateTime (encoding = w3cdtf); (qualifier = exact); (point = end)
2021-05-30
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after May 30th, 2021.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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ETD
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windows xp
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2019-04-02T21:11:07
DateCreated (point = end); (encoding = w3cdtf); (qualifier = exact)
2019-04-02T21:11:07
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