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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:BACKGROUND:Phthalates are known endocrine disruptors and peroxisome proliferator-activated receptor (PPAR) activators, potentially capable of promoting an obesogenic effect. Pregnant women are especially vulnerable to phthalate exposure due to physiological and metabolic changes during pregnancy, including those related to the metabolism of xenobiotics. Phthalate exposure during pregnancy has been associated with early gestational weight gain, however, its effect on long-term weight gain remains unclear. The aim of the present study was to evaluate the association between phthalate exposure during pregnancy and long-term changes in weight among women. METHODS:Urinary phthalate concentrations, socioeconomic, anthropometry and information on diet and socioeconomic status were collected during pregnancy from 178 women from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) birth cohort. Maternal body weight and diet information was also collected up to 5 times in the first year postpartum and twice during follow-up visits 5.2-10.7 years later. A path analysis was performed to assess associations between urinary phthalate metabolite levels during pregnancy and change in weight (kg) per year after delivery, including age, education, living with/without partner, parity, daily energy intake and breastfeeding duration. RESULTS:The mean age at pregnancy was 27.3?±?5.9 years and mean body mass index during the first postpartum year was 27.07?±?4.22?kg/m2. On average, women gained 3.48?kg (0.52?±?0.84?kg/year). A unit increase in log-transformed mono-3-carboxypropyl phthalate (MCPP) was associated with 0.33?kg (95% CI: 0.09, 0.56) higher weight gain per year, and mono-benzyl phthalate (MBzP) with 0.21?kg (95% CI: -0.38, -0.03) lower weight gain per year. CONCLUSION:Exposure to certain phthalates during pregnancy may be associated with long-term weight change in women. More studies on the effects of phthalate exposure during pregnancy on women's long-term health are required.

Dataset Information

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

Publications

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

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