Parental exposure to 1,2-benzisothiazol-3(2 H)-one induces intergenerational cardiac and ocular development toxicity in F1 zebrafish.

Abstract

1,2-Benzisothiazol-3(2 H)-one (BIT) is a widely utilised preservative in industrial applications and has been frequently detected in aquatic environments. The widespread occurrence and potential bioaccumulation of BIT in the environment raise significant ecological concerns. Although previous studies have addressed the embryonic toxicity of BIT, the intergenerational toxicity stemming from parental exposure to BIT remain inadequately understood. This study exposed parental zebrafish to BIT (300 ng/L and 300 μg/L) for 120 days to investigate its impact on the F1 generation, focusing on embryonic development, histopathology, and transcriptomic profiling through comprehensive phenotypic and molecular assessments. Our results demonstrated that parental BIT exposure did not significantly affect hatchability or mortality in the F1 offspring. However, it resulted in significant developmental impairments in F1 larvae, manifested as increased deformity rates (yolk sac edema, shortened body length), cardiovascular developmental disorders (pericardial edema, increased Bulbus Arteriosus-Sinus Venosus distance, and decreased heart rate, blood flow velocity, and blood pressure), and ocular and visual developmental disorders (decreased ocular area, reduced movement velocity, and reduced total movement distance). RNA-sequencing analysis revealed a significant enrichment of pathways associated with cardiac muscle contraction, cardiac morphogenesis, and ocular development. Transcriptomic analysis identified organ-specific transcriptional alterations in F1 larvae, including the dysregulation of genes essential for heart development (vmhcl, cox4i1l, bag3, brk1) and ocular development (opn1mw2, arr3a, arr3b). Our findings indicate that parental BIT exposure can lead to embryonic developmental defects in F1 larvae, thereby providing novel insights into the intergenerational toxicity of BIT.