Effects of combined exposure to 17α-methyltestosterone and polystyrene microplastics on lipid metabolism and the nervous system in Danio rerio

Polystyrene (PS) microplastics are pervasive environmental pollutants that are harmful to aquatic organisms upon degradation. The synthetic androgen 17α-methyltestosterone (MT) is an environmental endocrine-disrupting chemical. This study aimed to systematically evaluate the combined histological and molecular effects of MT and PS exposure on the liver and brain tissues of Danio rerio with focus on lipid metabolism and neural function disruption. Female D. rerio were exposed to 50 ng/L MT and 0.5 mg/L PS (5 μm in diameter) for 21 d. Histological observations, real-time quantitative PCR (qPCR), and RNA-sequencing (RNA-seq) analysis were employed to assess the effects of PS and MT. These results indicated that MT and PS co-exposure caused fatty degeneration of liver cells and a significant upregulation of lipid synthesis-related genes (ACSS1, CEL, FASN, and GK5). In brain tissue, the observed effects included reduced marginal layer neuron counts, cytoplasmic loosening of central layer neurons, disordered gray matter layer cells, and vascular congestion. RNA-seq analysis further revealed significant enrichment of differentially expressed genes in the "glycine, serine, and threonine metabolism" and "neuroactive ligand-receptor interaction" signaling pathways. Thus, MT and PS co-exposure induced lipid metabolism disorders in D. rerio and influence neural signaling by altering the "neuroactive ligand-receptor interaction" pathway. These findings highlight the complex risks posed by environmental pollutants to aquatic life and provide critical insights for environmental protection and aquatic health research.