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

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.

Linking the morphological and metabolomic response of Lactuca sativa L exposed to emerging contaminants using GC × GC-MS and chemometric tools

“…The connection of these metabolites with other pathways related to secondary metabolites (2,3-butanediol, tartrate, glycerate) may suggest an effect on the plants’ secondary metabolism, possibly related to their defence mechanisms, as occurs with embryos exposed to BPA 39–43 .…”

Bisphenol a and mesenchymal stem cells: Recent insights

“…Data from multiple sources have shown that the amount of BPA that humans are exposed to may cause adverse health effects, such as diabetes, obesity, abnormal neuronal behavior, developmental effects, and thyroid and reproductive disorders [58][59][60][61]. This has raised concerns among regulatory agencies all over the world [57].…”

The Role of Renin-Angiotensin-Aldosterone System in the Heart and Lung: Focus on COVID-19

“…The stimulation of the AT1 receptor induces vasoconstriction, increases the release of catecholamines and the synthesis of aldosterone (Unger, 2002), stimulates fibrosis and inflammation, and reduces the activity of collagenase and the expression of mitogen-activated protein kinase (MAPK) (Mascolo et al, 2017;Mascolo et al, 2020b). The proinflammatory action of AT1 receptors involves the downregulation of the NADPH oxidase expression in smooth muscle cells, the production of reactive oxygen species (ROS), and the activity of pro-inflammatory transcription nuclear factors like nuclear factor-kappaB (NF-κB) and E26 transformationspecific sequence (Ets) (Marchesi et al, 2008;Porreca et al, 2017). Moreover, these receptors induce the release of tumor necrosis factor-α (TNF-α), the interleukin-6 (IL-6), and the monocyte chemoattractant protein-1 (MCP-1) (Dandona et al, 2007) and shift the macrophage phenotype toward the proinflammatory M1 polarization state (Yamamoto et al, 2011).…”