RESUMEN
Tris(1,3-dichloro-2-propyl) phosphate (TCPP), a prevalent organophosphorus flame retardant in aquatic environments, has raised significant concerns regarding its ecological risks. This study aims to explore the impacts of TCPP on the reproductive functions of zebrafish and delineate its gender-related toxic mechanisms. By assessing the effects on zebrafish of 10 mg/L TCPP exposure from 30 to 120 days post-fertilization (dpf), we thoroughly evaluated the reproductive capability and endocrine system alterations. Our findings indicated that TCPP exposure disrupted gender differentiation in zebrafish and markedly impaired their reproductive capacity, resulting in decreased egg laying and offspring development quality. Histological analyses of gonadal tissues showed an abnormal increase in immature oocytes in females and a reduction in mature sperm count and spermatogonial structure integrity in males, collectively leading to compromised embryo quality. Additionally, molecular docking results indicated that TCPP showed a strong affinity for estrogen receptors, and TCPP-treated zebrafish exhibited imbalanced sex hormones and increased estrogen receptor expression. Alterations in genes associated with the hypothalamic-pituitary-gonadal (HPG) axis and activation of the steroidogenesis pathway suggested that TCPP targets the HPG axis to regulate sex hormone homeostasis. Tamoxifen (TAM), as a competitive inhibitor of estrogen, exhibited a biphasic effect, as evidenced by the counteraction of TCPP-induced effects in both male and female zebrafish after TAM addition. Overall, our study underscored the gender-dependent reproductive toxicity of TCPP exposure in zebrafish, characterized by diminished reproductive capacity and hormonal disturbances, likely due to interference in the HPG axis and steroidogenesis pathways. These findings emphasize the critical need to consider gender differences in chemical risk assessments for ecosystems and highlight the importance of understanding the mechanisms underlying the effects of chemical pollutants on the reproductive health of aquatic species.
RESUMEN
Triclosan (TCS) is a broad-spectrum antibiotic widely used in various personal care products. Research has found that exposure to TCS can cause toxic effects on organisms including neurotoxicity, cardiotoxicity, disorders of lipid metabolism, and abnormal vascular development, and the corresponding toxic mechanisms are gradually delving into the level of abnormal expression of miRNA regulating gene expression. Although the downstream mechanism of TCS targeting miRNA abnormal expression to induce toxicity is gradually improving, its upstream mechanism is still in a fog. Starting from the abnormal expression data of circRNA in zebrafish larvae induced by TCS, this study conducted a hierarchical analysis of the expression levels of all circRNAs, differential circRNAs, and trend circRNAs, and identified 29 key circRNA events regulating miRNA abnormal expression. In combination with GO and KEGG, the effects of TCS exposure were analyzed from the function and signaling pathway of the corresponding circRNA host gene. Furthermore, based on existing literature evidence about the biological toxicity induced by TCS targeting miRNA as data support, a competing endogenous RNAs (ceRNA) network characterizing the regulatory relationship between circRNA and miRNA was constructed and optimized. Finally, a comprehensive Adverse Outcome Pathway (AOP) framework of multiple levels of events including circRNA, miRNA, mRNA, pathway, and toxicity endpoints was established to systematically elucidate the toxic mechanism of TCS. Moreover, the rationality of the AOP framework was verified from the expression level of miRNA and adverse outcomes such as neurotoxicity, cardiotoxicity, oxidative stress, and inflammatory response by knockdown of circRNA48. This paper not only provides the key circRNA events for exploring the upstream mechanism of miRNA regulating gene expression but also provides an AOP framework for comprehensively demonstrating the toxicity mechanism of TCS on zebrafish, which is a theoretical basis for subsequent hazard assessment and prevention and control of TCS.