Maternal exposure to tris (2-butoxyethyl) phosphate induces F0 female reproductive toxicity and offspring developmental toxicity in zebrafish

The toxicity of tris (2-butoxyethyl) phosphate (TBOEP) has been extensively investigated because of its prevalence in the environment. Nevertheless, the risk factors associated with maternal transmission are poorly understood. In this study, sexually mature female zebrafish were treated with TBOEP (0, 20, 100, and 500 μg/L) for 30 days and were mated with unexposed males. Reproduction impairment in exposed adults (F0), including retarded gonado-somatic index (GSI), delayed oocyte maturation, inhibition of reproductive behavior, and subfertility was found. The observed impacts on the F0 generation were linked to a marked decrease in 17β-estradiol concentrations and disruptions in the gene expression patterns along the hypothalamic-pituitary-gonadal-liver (HPGL) axis. Moreover, the accumulation of TBOEP in F0 and their embryos (F1) was observed, indicating significant maternal transfer of TBOEP to the offspring. In F1 larvae, a dose-dependent increase in developmental toxicity (decreased heart rate and swimming behavior, increased larval mortality, and deformity) was observed. Additionally, a notable reduction in protein level in eggs and the gene expression of both the hormone/insulin-like growth factor (GH/IGF) and hypothalamic-pituitary-thyroid (HPT) pathways were observed. These results indicated that subacute TBOEP exposure could induce reproductive toxicity in female zebrafish and cause transgenerational toxicity in their offspring via maternal transfer.