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dc.contributor.author
Chamorro-Garcia, Raquel
dc.contributor.author
Diaz-Castillo, Carlos
dc.contributor.author
Shoucri, Bassem M.
dc.contributor.author
Käch, Heidi
dc.contributor.author
Leavitt, Ron
dc.contributor.author
Shioda, Toshi
dc.contributor.author
Blumberg, Bruce
dc.date.accessioned
2018-01-25T16:47:45Z
dc.date.available
2017-12-28T03:41:44Z
dc.date.available
2018-01-25T16:47:45Z
dc.date.issued
2017
dc.identifier.other
10.1038/s41467-017-01944-z
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/224730
dc.identifier.doi
10.3929/ethz-b-000224730
dc.description.abstract
Ancestral environmental exposures to non-mutagenic agents can exert effects in unexposed descendants. This transgenerational inheritance has significant implications for understanding disease etiology. Here we show that exposure of F0 mice to the obesogen tributyltin (TBT) throughout pregnancy and lactation predisposes unexposed F4 male descendants to obesity when dietary fat is increased. Analyses of body fat, plasma hormone levels, and visceral white adipose tissue DNA methylome and transcriptome collectively indicate that the F4 obesity is consistent with a leptin resistant, thrifty phenotype. Ancestral TBT exposure induces global changes in DNA methylation and altered expression of metabolism-relevant genes. Analysis of chromatin accessibility in F3 and F4 sperm reveals significant differences between control and TBT groups and significant similarities between F3 and F4 TBT groups that overlap with areas of differential methylation in F4 adipose tissue. Our data suggest that ancestral TBT exposure induces changes in chromatin organization transmissible through meiosis and mitosis.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Nature Publishing Group
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.title
Ancestral perinatal obesogen exposure results in a transgenerational thrifty phenotype in mice
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
dc.date.published
2017-12-08
ethz.journal.title
Nature Communications
ethz.journal.volume
8
en_US
ethz.journal.issue
1
en_US
ethz.pages.start
2012
en_US
ethz.size
13 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
London
en_US
ethz.publication.status
published
en_US
ethz.date.deposited
2017-12-28T03:41:53Z
ethz.source
SCOPUS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2018-01-25T16:47:51Z
ethz.rosetta.lastUpdated
2019-02-02T14:12:10Z
ethz.rosetta.exportRequired
true
ethz.rosetta.versionExported
true
ethz.COinS
ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.atitle=Ancestral%20perinatal%20obesogen%20exposure%20results%20in%20a%20transgenerational%20thrifty%20phenotype%20in%20mice&rft.jtitle=Nature%20Communications&rft.date=2017&rft.volume=8&rft.issue=1&rft.spage=2012&rft.au=Chamorro-Garcia,%20Raquel&Diaz-Castillo,%20Carlos&Shoucri,%20Bassem%20M.&K%C3%A4ch,%20Heidi&Leavitt,%20Ron&rft.genre=article&
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