Dysregulation of G protein-coupled receptors in the intestine by nanoplastic exposure in Caenorhabditis elegans

After their uptake, environmental toxicants may cause toxicity to organisms by activating or inhibiting certain G protein-coupled receptors (GPCRs). Nevertheless, the roles of GPCRs in mediating the response of organisms to nanoplastic exposure are still largely unclear. We here employed Caenorhabditis elegans as an animal model and focused on the identification of intestinal GPCRs required for control of the toxicity of nanopolystyrene (100 nm). Based on gene expression and functional analysis, we identified 13 GPCRs (PAQR-2, NPR-1, DOP-2, CED-1, NPR-9, FSHR-1, DCAR-1, NPR-12, NPR-4, SER-4, DAF-37, GTR-1, and NPR-8) involved in the control of nanopolystyrene toxicity. Moreover, among these identified GPCRs, only PAQR-2 and FSHR-1 acted in the intestine to regulate nanopolystyrene toxicity. PAQR-2 and FSHR-1 regulated nanopolystyrene toxicity in the intestine by at least modulating the activities of insulin, Wnt, p38 mitogen-activated protein kinase (MAPK), ELT-2, and/or mitochondrial unfolded protein response (mt UPR) signaling pathways. Therefore, our results provide a crucial basis for understanding the functions of GPCRs in the intestine to mediate the response to nanoplastic exposure in organisms.