Molecular targets of developmental exposure to bisphenol A in diabesity: a focus on endoderm-derived organs

Obes Rev. 2017 Jan;18(1):99-108. doi: 10.1111/obr.12471. Epub 2016 Oct 24.

Abstract

Several studies associate foetal human exposure to bisphenol A (BPA) to metabolic/endocrine diseases, mainly diabesity. They describe the role of BPA in the disruption of pancreatic beta cell, adipocyte and hepatocyte functions. Indeed, the complexity of the diabesity phenotype is due to the involvement of different endoderm-derived organs, all targets of BPA. Here, we analyse this point delineating a picture of different mechanisms of BPA toxicity in endoderm-derived organs leading to diabesity. Moving from epidemiological data, we summarize the in vivo experimental data of the BPA effects on endoderm-derived organs (thyroid, pancreas, liver, gut, prostate and lung) after prenatal exposure. Mainly, we gather molecular data evidencing harmful effects at low-dose exposure, pointing to the risk to human health. Although the fragmentation of molecular data does not allow a clear conclusion to be drawn, the present work indicates that the developmental exposure to BPA represents a risk for endoderm-derived organs development as it deregulates the gene expression from the earliest developmental stages. A more systematic analysis of BPA impact on the transcriptomes of endoderm-derived organs is still missing. Here, we suggest in vitro toxicogenomics approaches as a tool for the identification of common mechanisms of BPA toxicity leading to the diabesity in organs having the same developmental origin.

Keywords: Bisphenol A; endoderm-derived organs; epigenetics; perinatal exposure.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzhydryl Compounds / toxicity*
  • Diabetes Mellitus, Type 2 / chemically induced
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Disease Models, Animal
  • Endoderm / drug effects*
  • Gastrointestinal Tract / drug effects
  • Humans
  • Liver / drug effects
  • Lung / drug effects
  • Male
  • Metabolic Diseases / chemically induced
  • Metabolic Diseases / physiopathology*
  • Obesity / chemically induced
  • Obesity / physiopathology*
  • Pancreas / drug effects
  • Phenols / toxicity*
  • Prostate / drug effects
  • Thyroid Gland / drug effects

Substances

  • Benzhydryl Compounds
  • Phenols
  • bisphenol A