Abstract
BACKGROUND: Tris (2-chloroethyl) phosphate (TCEP), a widely used flame retardant, is widespread in the environment and potentially harmful to organisms. However, the specific mechanisms of TCEP-induced neurological and reproductive toxicity in fish are largely unknown. Turbot (Scophthalmus maximus) is cultivated on a large scale, and the emergence of pollutants with endocrine disrupting effects seriously affects its economic benefits. This study aimed to investigate the toxic effects of TCEP on turbot by integrating physio-biochemical and transcriptomic analyses. RESULTS: TCEP exposure induced severe neuroendocrine disrupting effects in turbot. Firstly, the hormone levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), and 11-ketotestosterone (11-KT) were significantly decreased under prolonged TCEP stress, which may have a negative impact on normal reproductive function. We identified and summarized representative differentially expressed genes (DEGs) and their functions, such as endocrine system and oxidative stress. Pathway enrichment showed that the toxicological characteristics of TCEP on turbot were neuroendocrine regulation disorders, including oxidative phosphorylation, apoptosis, steroid biosynthesis, GnRH signaling pathway and so on. Weighted gene co-expression network analysis (WGCNA) also revealed key genes involved in these pathways. Among these genes, those encoding the components of the electron transport chain presented an initial increase in expression followed by a decrease, indicating that TCEP stress might affect mitochondrial function and lead to cell damage. This finding was also supported by the upregulation of apoptosis-related gene expression. Moreover, acute exposure to TCEP regulated MAPK-mediated transduction and regulation of GnRH signaling, thereby altering the expression of hypothalamic-pituitary-gonadal (HPG) axis-related genes. CONCLUSIONS: These findings revealed the endocrine disrupting effects of TCEP on turbot and identified biomarkers related to reproductive toxicity, providing early warning for the monitoring of healthy aquaculture.