N⁶-methyladenosine RNA methylation regulates microplastics-induced cell senescence in the rainbow trout liver

Microplastics are prevalent in aquatic ecosystems, impacting various forms of aquatic life, including fish. In this study, Rainbow trout (Oncorhynchus mykiss) were exposed to two concentrations of microplastics (0 and 500 μg/L) over a 14-day period, during which a comprehensive analysis was conducted to assess the liver accumulation of microplastics and their effects on oxidative stress, the liver response, and transcriptomics. Our findings indicated that microplastics significantly accumulated in the liver and activated the antioxidant system in fish by enhancing the activity of antioxidant enzymes. Histological lesions were also observed in the liver of the fish. Furthermore, microplastics induced alterations in the expression of hepatic N⁶-methyladenosine readers, specifically downregulating IGF2BP1 (encoding insulin like growth factor 2 mRNA binding protein 1) and upregulating YTHDF2 (encoding YTH N⁶-methyladenosine RNA binding protein F2), which in turn decreased mRNA stability and reduced the expression of C-myc and other regulatory factors involved in the cell cycle and proliferation. This sequence of events resulted in slowed cell proliferation, the induction of cell cycle arrest, and the promotion of cellular senescence. This study offers valuable insights into the toxicological mechanisms of microplastics and enhances our understanding of the threats that plastic pollution poses to freshwater organisms.