Endocrine-disrupting chemicals (EDCs) are exogenous substances (xenobiotics) that affect the function of the endocrine system and cause health problems. These compounds are a wide range of synthetic or natural chemicals that mimic hormones and interact with endocrine receptors as agonists or antagonists, in trace amounts.

A variety of chemicals applied in industry such as solvents, lubricants, plasticizers, pharmaceutical agents, and flame retardants are endocrine disruptors as well as compounds used in agriculture including organophosphorus pesticides, organochlorine pesticides, and herbicides. These compounds are used widely and spread in the environment. They enter the food chain and infiltrate plants, animals, and humans, causing adverse effects, even at low concentrations. Exposure to EDCs can lead to a higher risk of obesity, nonalcoholic fatty liver disease, insulin resistance, type 2 diabetes mellitus, and endocrine-related cancers. They have also been linked to psychological disorders such as autism, cognitive difficulties, and abnormal social behavior.

Understanding the mechanisms and pathways underlying the impact of EDCs on the endocrine system and related adaptation or detoxification processes is essential to protect the body against them. Detoxification is a three-phase process involving transportation, oxidation, and metabolism; and xenosensors or xeno-sensing receptors play a pivotal role not only in the detection, but also in the detoxification and biotransformation, of xenobiotics.

Xenosensors are DNA-attached proteins capable of interacting with xenobiotics, including EDCs, as their ligands. Protein-ligand interaction activates the expression of specific genes and related metabolizing enzymes such as cytochrome P450s, that might be applied as early-stage biomarkers of EDC exposure. Xenosensors regulate various endogenous processes and signaling pathways, and EDC exposure may disrupt the regulation of cell function as a result.

Several types of xenosensors have been identified already. These include the constitutive androstane receptor (CAR), the pregnane X receptor (PXR), the peroxisome proliferator activated receptor (PPAR) and the retinoid X receptor (RXR). Some hormone receptors are also xenosensors, for example: estrogen receptors (ER), estrogen-related receptor (ERR), androgen receptor (AR), and thyroid receptor (TR). Despite this, further studies are required to determine whether other the nuclear and hormone receptors including the glucocorticoid receptor (GR) and the farnesoid X receptor (FXR), amongst others, are targets of EDCs.

Moreover, investigation into the unknown characteristics of xenosensor interactions with specific EDCs; and the molecular mechanisms of EDC biotransformation and metabolism aided by xenosensors, will be of interest. To achieve this goal, researchers may quantify the expression of xenosensors and their target genes or evaluate the complete transcriptome of a cell or tissue to provide a thorough understanding of gene expression changes in response to EDC exposure. This may lead to finding new xenosensors and their targeted genes, as well as to understand the ways that EDCs generally affect gene expression. Activation and expression of xenosensors and their downstream target proteins in response to EDCs provide valuable information that may lead to finding biomarkers used to evaluate body exposure to an individual or a group of EDCs.

Thus, we welcome: Original Research (experimental or in-silico) and Systematic or narrative Review articles based on the following potential topics and other related studies:

˗ Identification and characterization of xenosensors and their ligands

˗ Mechanisms of xenosensors activation and regulation

˗ Effects of EDCs on xenosensors expression and function

˗ The interaction between xenosensors and other signaling pathways in response to EDCs

˗ The susceptibility to EDCs and the genetic variation in xenosensors

˗ Development of novel methods to study xenosensors and EDC interactions

˗ Applications of xenosensors in environmental and human health risk assessment of EDCs

˗ Identifying new biomarkers to detect exposure to EDCs

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Frontiers in Endocrinology

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