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- Title
<italic>MEST</italic> mediates the impact of prenatal bisphenol A exposure on long-term body weight development.
- Authors
Junge, Kristin M.; Leppert, Beate; Jahreis, Susanne; Wissenbach, Dirk K.; Feltens, Ralph; Grützmann, Konrad; Thürmann, Loreen; Bauer, Tobias; Ishaque, Naveed; Schick, Matthias; Bewerunge-Hudler, Melanie; Röder, Stefan; Bauer, Mario; Schulz, Angela; Borte, Michael; Landgraf, Kathrin; Körner, Antje; Kiess, Wieland; von Bergen, Martin; Stangl, Gabriele I.
- 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 (<italic>n</italic> = 552), and BPA-associated changes in cord blood DNA methylation were analyzed by Illumina Infinium HumanMethylation450 BeadChip arrays (<italic>n</italic> = 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) <italic>z</italic> 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 (<italic>n</italic> ≥ 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 (<italic>n</italic> = 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 (<italic>MEST)</italic>. A mediator analysis suggested that prenatal BPA exposure was connected to cord blood <italic>MEST</italic> promoter methylation and <italic>MEST</italic> expression as well as BMI <italic>z</italic> scores in early infancy. This effect could be confirmed in mice in which prenatal BPA exposure altered <italic>Mest</italic> 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 <italic>MEST</italic> expression and enhanced adipogenesis following BPA exposure. Conclusions: Our study provides evidence that <italic>MEST</italic> mediates the impact of prenatal BPA exposure on long-term body weight development in offspring by triggering adipocyte differentiation.
- Subjects
PHYSIOLOGICAL effects of chemicals; BISPHENOL A; DNA methylation; OBESITY
- Publication
Clinical Epigenetics, 2018, Vol 10, Issue 1, pN.PAG
- ISSN
1868-7075
- Publication type
Article
- DOI
10.1186/s13148-018-0478-z