% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@ARTICLE{Junge:132912,
author = {K. M. Junge and B. Leppert and S. Jahreis and D. K.
Wissenbach and R. Feltens and K. Grützmann$^*$ and L.
Thürmann and T. Bauer$^*$ and N. Ishaque$^*$ and M.
Schick$^*$ and M. Bewerunge-Hudler$^*$ and S. Röder and M.
Bauer and A. Schulz and M. Borte and K. Landgraf and A.
Körner and W. Kiess and M. von Bergen and G. I. Stangl and
S. Trump and R. Eils$^*$ and T. Polte and I. Lehmann},
title = {{MEST} mediates the impact of prenatal bisphenol {A}
exposure on long-term body weight development.},
journal = {Clinical epigenetics},
volume = {10},
number = {1},
issn = {1868-7083},
address = {[S.l.]},
publisher = {BioMed Central},
reportid = {DKFZ-2018-00554},
pages = {58},
year = {2018},
abstract = {Exposure to endocrine-disrupting chemicals can alter normal
physiology and increase susceptibility to non-communicable
diseases like obesity. Especially the prenatal and early
postnatal period is highly vulnerable to adverse effects by
environmental exposure, promoting developmental
reprogramming by epigenetic alterations. To obtain a deeper
insight into the role of prenatal bisphenol A (BPA) exposure
in children's overweight development, we combine
epidemiological data with experimental models and
BPA-dependent DNA methylation changes.BPA concentrations
were measured in maternal urine samples of the LINA
mother-child-study obtained during pregnancy (n = 552),
and BPA-associated changes in cord blood DNA methylation
were analyzed by Illumina Infinium HumanMethylation450
BeadChip arrays (n = 472). Methylation changes were
verified by targeted MassARRAY analyses, assessed for their
functional translation by qPCR and correlated with
children's body mass index (BMI) z scores at the age of 1
and 6 years. Further, female BALB/c mice were exposed to
BPA from 1 week before mating until delivery, and weight
development of their pups was monitored (n ≥ 8/group).
Additionally, human adipose-derived mesenchymal stem cells
were treated with BPA during the adipocyte differentiation
period and assessed for exposure-related epigenetic,
transcriptional and morphological changes (n = 4).In
prenatally BPA-exposed children two CpG sites with deviating
cord blood DNA-methylation profiles were identified, among
them a hypo-methylated CpG in the promoter of the
obesity-associated mesoderm-specific transcript (MEST). A
mediator analysis suggested that prenatal BPA exposure was
connected to cord blood MEST promoter methylation and MEST
expression as well as BMI z scores in early infancy. This
effect could be confirmed in mice in which prenatal BPA
exposure altered Mest promoter methylation and transcription
with a concomitant increase in the body weight of the
juvenile offspring. An experimental model of in vitro
differentiated human mesenchymal stem cells also revealed an
epigenetically induced MEST expression and enhanced
adipogenesis following BPA exposure.Our study provides
evidence that MEST mediates the impact of prenatal BPA
exposure on long-term body weight development in offspring
by triggering adipocyte differentiation.},
cin = {L301 / B080 / W110},
ddc = {610},
cid = {I:(DE-He78)L301-20160331 / I:(DE-He78)B080-20160331 /
I:(DE-He78)W110-20160331},
pnm = {312 - Functional and structural genomics (POF3-312)},
pid = {G:(DE-HGF)POF3-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:29721103},
pmc = {pmc:PMC5910578},
doi = {10.1186/s13148-018-0478-z},
url = {https://inrepo02.dkfz.de/record/132912},
}