Publication Details

Category Text Publication
Reference Category Journals
DOI 10.1186/s13148-018-0478-z
Licence creative commons licence
Title (Primary) MEST mediates the impact of prenatal bisphenol A exposure on long-term body weight development
Author Junge, K.M.; Leppert, B.; Jahreis, S.; Wissenbach, D.K.; Feltens, R.; Grützmann, K.; Thürmann, L.; Bauer, T.; Ishaque, N.; Schick, M.; Bewerunge-Hudler, M.; Röder, S. ORCID logo ; Bauer, M.; Schulz, A.; Borte, M.; Landgraf, K.; Körner, A.; Kiess, W.; von Bergen, M.; Stangl, G.I.; Trump, S.; Eils, R.; Polte, T.; Lehmann, I.
Source Titel Clinical Epigenetics
Year 2018
Department IMMU; METABOX; MOLSYB
Volume 10
Page From art. 58
Language englisch
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Keywords EDC – Prenatal exposure – Infants – Obesity – LINA – Mice – Mesenchymal stem cells – Epigenetics – DNA methylation – Adipogenesis
Abstract

Background

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.

Methods

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).

Results

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.

Conclusions

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.

Persistent UFZ Identifier https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=20268
Junge, K.M., Leppert, B., Jahreis, S., Wissenbach, D.K., Feltens, R., Grützmann, K., Thürmann, L., Bauer, T., Ishaque, N., Schick, M., Bewerunge-Hudler, M., Röder, S., Bauer, M., Schulz, A., Borte, M., Landgraf, K., Körner, A., Kiess, W., von Bergen, M., Stangl, G.I., Trump, S., Eils, R., Polte, T., Lehmann, I. (2018):
MEST mediates the impact of prenatal bisphenol A exposure on long-term body weight development
Clin. Epigenetics 10 , art. 58 10.1186/s13148-018-0478-z