The comparative toxicities of BPA, BPB, BPS, BPF, and BPAF on the reproductive neuroendocrine system of zebrafish embryos and its mechanisms

Bisphenol A (BPA) is a well-known endocrine disruptor that has elicited great concern because of its potential toxic effects in organisms. In this study, the effects of BPA and several BPA structural analogs, including BPB, BPS, BPF, and BPAF, on the reproductive neuroendocrine system were evaluated during zebrafish embryonic and larval development. Our results showed that the numbers of gonadotropin-releasing hormone 3 neurons in zebrafish embryos increased after 100 μg/L BPA analog treatment, and exposure to BPA or its analogs at 1 or 100 μg/L increased the expression of reproductive neuroendocrine-related genes and the levels of typical hormones such as LH, FSH, E2, and GH. Moreover, the effects were associated with increases in the activities of erα, erβ, and cyp19a genes. The respective estrogen receptors (ER) and aromatase (AROM) antagonists significantly attenuated the stimulation of lhβ, fshβ, LH, and FSH expression, thereby proving that BPA analogs affect the reproductive neuroendocrine system via ERs and AROM pathway. Furthermore, we observed that the reproductive neuroendocrine toxicity of BPAF was more similar to that of BPA. This was the first study to comparatively explore the reproductive neuroendocrine toxicities of bisphenols in aquatic organism.