Environmental level of bisphenol F induced reproductive toxicity toward zebrafish

Bisphenol F (BPF), as an important bisphenol A substitute, is being increasingly used for industrial production. Here we performed large scale fecundity test for zebrafish that are continuous exposed to environmental levels of BPF (0.5, 5 and 50 μg/L) from embryonic stage, and identified suppressed spawning capacity of females and reduced fertility rate of males in adulthood. Although pathological change is only observed in female gonads, the transcriptional change in the hypothalamic-pituitary-gonad axis genes occurred in the gonads of both female and male fish at 150 days post-exposure. F1 generation embryos showed abnormal developmental outcomes including decreased heart rate, reduced body length, and inhibition of spontaneous movement after parental exposure to BPF. RNA-sequencing showed that the genes involved in skeletal/cardiac muscle development were significantly altered in F1 embryos spawned by BPF-treated zebrafish. The advanced pathway analysis showed that cancer and tumour formation were the most enriched pathways in the offspring of 0.5 and 5.0 μg/L groups; organismal development and cardiovascular system development were mainly affected after parental exposure to 50 μg/L of BPF; these changes were mediated by several involved regulators such as GATA4, MYF6, and MEF2C. These findings confirmed that long-term exposure to BPF at environment relevant concentration would result in reproductive toxicity among zebrafish indicating the urgent demand for the control of BPA substitutes.