Molecular mechanism of endocrine-disruptive effects induced by Bisphenol A: The role of transmembrane G-protein estrogen receptor 1 and integrin αvβ3

• Published in: Journal of environmental sciences (China) Vol. 75; pp. 1 - 13
• Main Authors: Sheng, Zhiguo, Wang, Cong, Ren, Furong, Liu, Yuxiang, Zhu, Benzhan
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.01.2019
• Subjects: Benzhydryl Compounds - toxicity; Bisphenol A; Endocrine Disruptors - toxicity; G protein-coupled estrogen receptor 1; Integrin alphaVbeta3 - metabolism; Integrin αvβ3; Low-dose effects; Phenols - toxicity; Receptors, Estrogen - metabolism; Receptors, G-Protein-Coupled - metabolism; Reproductive toxicity; Thyroxine interference effect; Bisphenol A; Integrin αvβ3; Low-dose effects; G protein-coupled estrogen receptor 1; Thyroxine interference effect; Reproductive toxicity
• ISSN: 1001-0742; 1878-7320
• DOI: 10.1016/j.jes.2018.05.002

Bisphenol A (BPA) is one of the highest volume industrial products worldwide and has been widely used to make various products as the intermediates of polycarbonate plastics and epoxy resins. Inevitably, general population has been widely exposed to BPA due to extensive use of BPA-containing products. BPA has similar chemical structure with the natural estrogen and has been shown to induce a variety of estrogen-like endocrine effects on organism in vivo or in vitro. High doses of BPA tend to act as antagonist of estrogen receptors (ERs) by directly regulating the genomic transcription. However, BPA at environmentally relevant low-dose always disrupt the biological function via a non-genomic manner mediated by membrane receptors, rather than ERs. Although some studies had investigated the non-genomic effects of low-dose BPA, the exact molecular mechanism still remains unclear. Recently, we found that membrane G protein-coupled estrogen receptor 1 and integrin αvβ3 and its relative signal pathways participate in the induction of male germ cell proliferation and thyroid transcription disruption by the low-dose BPA. A profound understanding for the mechanism of action of the environmentally relevant BPA exposure not only contributes to objectively evaluate and predict the potential influence to human health, but also provides theoretical basis and methodological support for assessing health effects trigged by other estrogen-like environmental endocrine disruptors. Based mainly on our recent findings, this review outlines the research progress of molecular mechanism on endocrine disrupting effects of environmental low-dose BPA, existing problems and some consideration for future studies. [Display omitted]