Dataset Information

Prenatal Bisphenol A Exposure in Mice Induces Multitissue Multiomics Disruptions Linking to Cardiometabolic Disorders.

ABSTRACT: The health impacts of endocrine-disrupting chemicals (EDCs) remain debated, and their tissue and molecular targets are poorly understood. In this study, we leveraged systems biology approaches to assess the target tissues, molecular pathways, and gene regulatory networks associated with prenatal exposure to the model EDC bisphenol A (BPA). Prenatal BPA exposure at 5 mg/kg/d, a dose below most reported no-observed-adverse-effect levels, led to tens to thousands of transcriptomic and methylomic alterations in the adipose, hypothalamus, and liver tissues in male offspring in mice, with cross-tissue perturbations in lipid metabolism as well as tissue-specific alterations in histone subunits, glucose metabolism, and extracellular matrix. Network modeling prioritized main molecular targets of BPA, including Pparg, Hnf4a, Esr1, Srebf1, and Fasn as well as numerous less studied targets such as Cyp51 and long noncoding RNAs across tissues, Fa2h in hypothalamus, and Nfya in adipose tissue. Lastly, integrative analyses identified the association of BPA molecular signatures with cardiometabolic phenotypes in mouse and human. Our multitissue, multiomics investigation provides strong evidence that BPA perturbs diverse molecular networks in central and peripheral tissues and offers insights into the molecular targets that link BPA to human cardiometabolic disorders.

SUBMITTER: Shu L

PROVIDER: S-EPMC6349005 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Prenatal Bisphenol A Exposure in Mice Induces Multitissue Multiomics Disruptions Linking to Cardiometabolic Disorders.

Shu Le L Meng Qingying Q Diamante Graciel G Tsai Brandon B Chen Yen-Wei YW Mikhail Andrew A Luk Helen H Ritz Beate B Allard Patrick P Yang Xia X

Endocrinology 20190201 2

The health impacts of endocrine-disrupting chemicals (EDCs) remain debated, and their tissue and molecular targets are poorly understood. In this study, we leveraged systems biology approaches to assess the target tissues, molecular pathways, and gene regulatory networks associated with prenatal exposure to the model EDC bisphenol A (BPA). Prenatal BPA exposure at 5 mg/kg/d, a dose below most reported no-observed-adverse-effect levels, led to tens to thousands of transcriptomic and methylomic al ...[more]

PMID: 30566610

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Project description:Background: How prenatal smoke exposure affects DNA methylation leading to atopic disorders remains to be addressed. Epigenetic biomarkers informative of prenatal smoke exposure and atopic disorders are wanting. Since most children suffering from atopic dermatitis (AD) continue to develop asthma later in life, we explored whether prenatal smoke exposure e induces DNA methylation and searched for predictive epigenetic biomarkers for smoke related atopic disorders. Methods: Methylation differences associated with smoke exposure were screened by Illumina methylation panel for children from the Taiwan birth panel study cohort initially. Information about development of atopic dermatitis (AD) and risk factors were collected. Cord blood cotinine levels were measured to represent prenatal smoke exposure. CpG loci that demonstrated a statistically significant difference in methylation were validated by methylation-dependent fragment separation (MDFS). Differential methylation in three genes (TSLP, GSTT1, and CYB5R3) was identified through the screen and their functions were investigated. Results: Among these, only thymic stromal lymphopoietin (TSLP) gene displayed significant difference in promoter methylation percentage after being validated by MDFS (p=0.029). TSLP gene was further investigated in a larger sample of 92 children from the cohort. Methylation status of the TSLP 5′-CpG island (CGI) was found to be significantly associated with prenatal smoke exposure (OR=3.59, 95%CI=1.49-8.64; cotinine level 0.10 ng/ml, sensitivity= 77%; specificity = 61%) and with AD (OR=4.77, 95%CI=1.47-15.53). The degree of TSLP 5′CGI methylation inversely correlated with TSLP protein expression levels (per unit: β=－6.69 ng/ml; 95% CIs, －12.80~－0.59; p=0.032). Conclusions: The effect of prenatal tobacco smoke exposure on the risk for AD may be mediated through DNA methylation. Cord blood methylated TSLP 5′CGI may be a potential epigenetic biomarker for environmentally-related atopic disorders. The buffy coat and plasma samples were separated and stored at −80°C. DNA (100 ng-500 ng) was extracted from cord white blood cells. Microarrays have been performed to investigate fourteen samples, which were classified as two groups according to cotinine exposure dosage (7 versus 7 : high exposure verses low exposure).

Dataset Information

Prenatal Bisphenol A Exposure in Mice Induces Multitissue Multiomics Disruptions Linking to Cardiometabolic Disorders.

Publications

Prenatal Bisphenol A Exposure in Mice Induces Multitissue Multiomics Disruptions Linking to Cardiometabolic Disorders.

Similar Datasets

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