Environmental Estrogens and Their Biological Effects through GPER Mediated Signal Pathways

Many environmental chemicals have been found to exert estrogenic effects in cells and experimental animals by activating nuclear receptors such as estrogen receptors and estrogen-related receptors. These compounds include bisphenols, pesticides, polybrominated diphenyl ethers (PBDEs), organophosphate flame retardants, phthalates and metalloestrogens. G protein-coupled estrogen receptor (GPER) exists widely in numerous cells/tissues of human and other vertebrates. A number of studies have demonstrated that GPER plays a vital role in mediating the estrogenic effects of environmental pollutants. Even at very low concentrations, these chemicals may activate GPER pathways, thus affect many aspects of cellular functions including proliferation, metastasis and apoptosis, resulting in cancer progression, cardiovascular disorders, and reproductive dysfunction. This review summarized the environmental occurrence and human exposure levels of these pollutants, and integrated current experimental evidence toward revealing the underlying mechanisms of pollutant-induced cellular dysfunction via GPER. The GPER mediated rapid non-genomic actions play an important role in the process leading to the adverse effects observed in experimental animals and even in human beings.