三氯卡班通过slc25a4的H3K27ac介导斑马鱼跨代发育毒性机制研究

Abstract

Triclocarban (TCC) is widely used in personal care products and medical disinfectants, and it was frequently detected in the environment and in humans. In this study, no abnormalities were observed in zebrafish (F0) during exposure to 1, 10, 100 μg/L of TCC (0-4 dpf). However, body length and weight were significantly suppressed at adulthood. Meanwhile, the number of spermatocytes and late-stage oocytes was reduced, and egg production was also decreased. Developmental defect phenotypes were observed in unexposed F1 generation during early life-stage. In addition, the developmental defect phenotypes were still observed in F2 and F3 generation. This indicated that TCC exhibited transgenerational developmental toxicity. RNA-seq results revealed that slc25a4 was significantly up-regulated and mitochondrial autophagy relative pathway was activated in F1-F3 generations. Treatment with Carboxyatractyloside (inhibitor of slc25a4 ) suppressed the expression of slc25a4 while attenuating the developmental defect phenotypes of F1-F3 generations. In addition, both hdac5 and hdac7 were down-regulated in F1-F3 generations. ChIP-PCR results indicated that H3K27ac levels were significantly increased in the promoter region of slc25a4 in F1-F3 generation. These results suggest that the up-regulation of slc25a4 induced by TCC is the key to the occurrence of the developmental defect phenotypes, and that H3K27ac of slc25a4 may mediate the transgenerational transmission of developmental defect phenotypes. This study provides new perspectives for evaluating the health safety and environmental risks of environmentally relevant doses of TCC.