Triclosan induces spermatogenic damage via the oxidative stress-P53-apoptosis pathway in zebrafish.

Triclosan (TCS), a widely used antimicrobial agent, has been identified as a reproductive endocrine disruptor. However, the mechanisms underlying TCS-induced gonadal damage remain incompletely understood. In this study, zebrafish were chronically exposed to TCS from 4 h post-fertilization (hpf) to 120 days post-fertilization (dpf). A comprehensive analysis was conducted, including assessment of testicular cell apoptosis in adult fish, evaluation of apoptosis-related genes and proteins in both adult testes and 50-day-old juveniles, and transcriptome sequencing. The results showed that TCS exposure downregulated mRNA expression of oxidative stress-related and anti-apoptotic genes, while upregulating pro-apoptotic gene expression along with P53 and Caspase 3 protein levels, ultimately leading to a significant increase in testicular apoptotic cells. Transcriptome sequencing analysis revealed enrichment of the P53 signaling pathway, apoptosis pathway, response to oxidative stress biological process. These findings indicate that postembryonic exposure to TCS causes gonadal damage primarily by inducing oxidative stress, which increases P53 expression, subsequently regulating pro-apoptotic gene expression and suppressing anti-apoptotic proteins, thereby activating the mitochondrial apoptosis pathway and death receptor pathway, potentially affecting growth, development, and reproductive toxicity. This study systematically elucidates the molecular mechanism by which TCS induces reproductive toxicity through the oxidative stress-P53 axis, which triggers both the mitochondrial and death receptor apoptotic pathways. Our findings provide important experimental evidence and a theoretical reference for the scientific assessment of TCS-related reproductive health risks.