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 mu g/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 in-cluding decreased heart rate, reduced body length, and inhibition of spontaneous movement after parental expo -sure 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 mu g/L groups; organismal development and cardiovascular system development were mainly affected after parental exposure to 50 mu g/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. (c) 2021 Elsevier B.V. All rights reserved.

Automated summary

Bisphenol F (BPF) had negative effects on the reproductive capacity and development of zebrafish, especially showing pathological changes in female gonads and affecting the fertility rate of male fish. Exposure to BPF led to abnormal development in F1 generation embryos and altered genes involved in skeletal/cardiac muscle development. The enriched pathways in the offspring varied depending on the BPF concentration, with regulators like GATA4, MYF6, and MEF2C mediating the observed changes.