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Lipid regulation of placental mycotoxin transport

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TitleInfo
Title
Lipid regulation of placental mycotoxin transport
Name (type = personal)
NamePart (type = family)
Szilagyi
NamePart (type = given)
John Thomas
NamePart (type = date)
1991-
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John Thomas Szilagyi
Role
RoleTerm (authority = RULIB)
author
Name (type = personal)
NamePart (type = family)
Buckley
NamePart (type = given)
Brian
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Brian Buckley
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Advisory Committee
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chair
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NamePart (type = family)
Aleksunes
NamePart (type = given)
Lauren
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Lauren Aleksunes
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Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Laskin
NamePart (type = given)
Jeffrey
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Jeffrey Laskin
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Roepke
NamePart (type = given)
Troy
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Troy Roepke
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Thompson
NamePart (type = given)
Kary
DisplayForm
Kary Thompson
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
outside 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 (qualifier = exact)
2018
DateOther (qualifier = exact); (type = degree)
2018-10
CopyrightDate (encoding = w3cdtf)
2018
Place
PlaceTerm (type = code)
xx
Language
LanguageTerm (authority = ISO639-2b); (type = code)
eng
Abstract (type = abstract)
During pregnancy, the placental BCRP/ABCG2 efflux transporter prevents the transplacental transfer of chemicals and protects the fetus from exposure to toxicants. Prior studies have demonstrated that BCRP can transport zearalenone, an estrogenic mycotoxin produced by fungi that grows on cereal crops. However, there is little known regarding the neonatal outcomes of compromised placental BCRP function in pregnant women exposed to zearalenone. Because of its estrogenic activity, in utero exposure to zearalenone could potentially increase the risk of altered sexual development and certain cancers. The purpose of this dissertation was to determine the influence of lipids on the expression and function of placental BCRP and its impact on the placental distribution of zearalenone during pregnancy. In both in vitro transwell models of the placental barrier (Marine Darby Canine Kidney cells and BeWo trophoblasts) and in vivo experiments with C57BL/6 mice, BCRP/Bcrp prevented the maternal-to-fetal transfer of zearalenone. Anandamide, an endocannabinoid, is known to influence placental development and function and may play a role in certain diseases of pregnancy. Studies using both human term placental explants and BeWo trophoblasts revealed that anandamide can down-regulate BCRP mRNA transcription and protein expression via a CB2-cyclic AMP signaling pathway. In BeWo trophoblast cells, anandamide increased the retention of Hoechst 33342, a fluorescent BCRP substrate, and zearalenone without directly inhibiting BCRP. Anandamide also decreased the basolateral-to-apical transport of glyburide, a BCRP substrate prescribed for gestational diabetes. Detailed analysis of human placenta specimens and BeWo trophoblasts also revealed that BCRP function is dependent on membrane cholesterol. Specifically, lipid raft isolation by density gradient ultracentrifugation demonstrated that BCRP is localized to lipid rafts in both BeWo trophoblasts and human placentas. Pre-treatment with cholesterol lowering agents pravastatin and methyl-β-cyclodextrin decreased BCRP efflux of both Hoechst 33342 and zearalenone without altering BCRP surface expression. Taken together, these data provide evidence that BCRP is important in protecting the fetus from exposure to zearalenone and that this function can be influenced by certain classes of lipids.
Subject (authority = RUETD)
Topic
Toxicology
Subject (authority = ETD-LCSH)
Topic
Mycotoxins
Subject (authority = ETD-LCSH)
Topic
Maternal-fetal exchange
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_9195
PhysicalDescription
Form (authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
1 online resource (242 pages : illustrations)
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Note (type = statement of responsibility)
by John Thomas Szilagyi
RelatedItem (type = host)
TitleInfo
Title
School of Graduate Studies Electronic Theses and Dissertations
Identifier (type = local)
rucore10001600001
Location
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NjNbRU
Identifier (type = doi)
doi:10.7282/t3-zqqc-t746
Genre (authority = ExL-Esploro)
ETD doctoral
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Rights

RightsDeclaration (ID = rulibRdec0006)
The author owns the copyright to this work.
RightsHolder (type = personal)
Name
FamilyName
SZILAGYI
GivenName
JOHN THOMAS
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2018-09-14 10:46:35
AssociatedEntity
Name
JOHN SZILAGYI
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)
2018-10-31
DateTime (encoding = w3cdtf); (qualifier = exact); (point = end)
2019-10-31
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after October 31st, 2019.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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2018-10-12T12:16:39
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2018-10-12T12:17:03
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