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MEST mediates the impact of prenatal bisphenol A exposure on long-term body weight development.

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.

SUBMITTER: Junge KM

PROVIDER: S-EPMC5910578 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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<i>MEST</i> mediates the impact of prenatal bisphenol A exposure on long-term body weight development.

Junge Kristin M KM Leppert Beate B Jahreis Susanne S Wissenbach Dirk K DK Feltens Ralph R Grützmann Konrad K Thürmann Loreen L Bauer Tobias T Ishaque Naveed N Schick Matthias M Bewerunge-Hudler Melanie M Röder Stefan S Bauer Mario M Schulz Angela A Borte Michael M Landgraf Kathrin K Körner Antje A Kiess Wieland W von Bergen Martin M Stangl Gabriele I GI Trump Saskia S Eils Roland R Polte Tobias T Lehmann Irina I

Clinical epigenetics 20180420

<h4>Background</h4>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 e ...[more]

PMID: 29721103

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Project description:BackgroundPhthalates are endocrine disrupting chemicals that may influence weight status; however, few studies have considered weight gain during pregnancy and subsequent long-term weight changes in women.ObjectiveTo determine associations of prenatal phthalate exposure with maternal weight during pregnancy and through up to seven years post-delivery.MethodsWe analyzed 15 urinary phthalate biomarker concentrations during the 2nd and 3rd trimesters among 874 pregnant women enrolled in the Programming Research in Obesity, Growth Environment and Social Stress Study in Mexico City. We examined three time-specific maternal weight outcomes: gestational weight gain (between 2nd and 3rd trimesters), short-term weight (between 3rd trimester and 12 months post-delivery), and long-term weight (between 18 months and 6-7 years post-delivery). We used Bayesian Kernel Machine Regression (BKMR) to estimate associations for the total phthalate mixture, as well as multivariable linear mixed models for individual phthalate biomarkers.ResultsAs a mixture, 2nd trimester urinary phthalate biomarker concentrations were associated with somewhat lower gestational weight gain between the 2nd and 3rd trimesters (interquartile range, IQR, difference: -0.07 standard deviations, SD; 95% credible interval, CrI: -0.20, 0.06); multivariable regression and BKMR models indicated that this inverse association was primarily driven by mono-2-ethyl-5-carboxypentyl terephthalate (MECPTP). Prenatal (2nd and 3rd trimesters) urinary phthalate mixture concentrations were positively associated with maternal weight change through 12 months postpartum (IQR difference: 0.11 SD; 95% CrI: 0.00, 0.23); these associations persisted from 18 months to 6-7 years follow-up (IQR difference: 0.07 SD; 95% CrI: 0.04, 0.10). Postpartum weight changes were associated with mono-3-carboxypropyl phthalate (MCPP) and MECPTP.ConclusionsPrenatal phthalate exposure was inversely associated with gestational weight gain and positively associated with long-term changes in maternal weight. Further investigation is required to understand how phthalates may influence body composition and whether they contribute to the development of obesity and other cardiometabolic diseases in women.

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MEST mediates the impact of prenatal bisphenol A exposure on long-term body weight development.

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<i>MEST</i> mediates the impact of prenatal bisphenol A exposure on long-term body weight development.

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MEST mediates the impact of prenatal bisphenol A exposure on long-term body weight development.

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&lt;i&gt;MEST&lt;/i&gt; mediates the impact of prenatal bisphenol A exposure on long-term body weight development.

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OmicsDI is part of the ELIXIR infrastructure

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<i>MEST</i> mediates the impact of prenatal bisphenol A exposure on long-term body weight development.