Prenatal Bisphenol A Exposure in Mice Induces Multitissue Multiomics Disruptions Linking to Cardiometabolic Disorders
| Autor: | Xia Yang, Helen Luk, Patrick Allard, Le Shu, Brandon L. Tsai, Yen-Wei Chen, Graciel Diamante, Qingying Meng, Andrew Mikhail, Beate Ritz |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty endocrine system Offspring Systems biology Gene regulatory network Hypothalamus Adipose tissue 030209 endocrinology & metabolism Endocrine Disruptors Epigenesis Genetic Transcriptome 03 medical and health sciences 0302 clinical medicine Endocrinology Phenols Pregnancy Internal medicine medicine Animals Benzhydryl Compounds Research Articles Metabolic Syndrome biology Lipid metabolism Phenotype Mice Inbred C57BL 030104 developmental biology Histone Adipose Tissue Liver Cardiovascular Diseases Prenatal Exposure Delayed Effects biology.protein Female hormones hormone substitutes and hormone antagonists Transcription Factors |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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