Bisphenol A (BPA) and bisphenol S (BPS) are implicated in the development of metabolic disorders, such diabetes mellitus. However, the epigenetic mechanism underlying the pancreatic β-cell dysregulation for both BPA/BPS needs clarification. This exploratory study was designed to investigate whether embryonic exposure to low BPA/BPS concentrations impair early pancreatic β-cell differentiation as well as DNA methylation in its gene expression profile using an in vivo model, zebrafish. Zebrafish embryos were exposed to 0, 0.01, 0.03, 0.1, 0.3, and 1.0 µM BPA/BPS at 4-h post fertilization (hpf) until 120 hpf. BPA/BPS-induced effects on pancreatic-related genes, insulin gene, and DNA methylation-associated genes were assessed at developmental stages (24–120 hpf), while glucose level was measure at the 120 hpf. The insulin expression levels decreased at 72–120 hpf for 1.0 µM BPA, while 0.32 and 0.24-fold of insulin expression were elicited by 0.3 and 1 µM BPS respectively at 72 hpf. Significant elevation of glucose levels; 16.3% (for 1.0 µM BPA), 7.20% (for 0.3 µM BPS), and 74.09% (for 1.0 µM BPS) higher than the control groups were observed. In addition, pancreatic-related genes pdx-1, foxa2, ptfla, and isl1 were significantly interfered compared with the untreated group. Moreover, the maintenance methylation gene, dnmt1, was monotonically and significantly decreased at early stage of development following BPA exposure but remained constant for BPS treatment relative to the control group. DNMT3a and DNMT3b orthologs were distinctively altered following BPA/BPS embryonic exposure. Our data indicated that embryonic exposure to low concentration of BPA/BPS can impair the normal expressions of pancreatic-associated genes and DNA methylation pattern of selected genes in zebrafish early development.

双酚A（BPA）和双酚S（BPS）与代谢紊乱的发展有关，例如糖尿病。然而，对于BPA / BPS的胰岛β细胞失调的表观遗传机制有待阐明。这项探索性研究旨在使用体内模型斑马鱼调查胚胎是否暴露于低BPA / BPS浓度是否会损害早期胰腺β细胞分化以及其基因表达谱中的DNA甲基化。受精（hpf）后4小时，斑马鱼胚胎暴露于0、0.01、0.03、0.1、0.3和1.0 µM BPA / BPS，直到120 hpf。BPA / BPS对胰腺相关基因，胰岛素基因和DNA甲基化相关基因的诱导作用在发育阶段（24–120 hpf）进行评估，而葡萄糖水平则在120 hpf进行测量。对于1.0 µM BPA，胰岛素表达水平在72–120 hpf下下降，而在72 hpf下，0.3和1 µM BPS分别引起0.32和0.24倍胰岛素表达。葡萄糖水平显着升高；观察到比对照组高16.3％（对于1.0 µM BPS），7.20％（对于0.3 µM BPS）和74.09％（对于1.0 µM BPS）。另外，胰腺相关基因PDX- 1，FOXA2，ptfla和ISL1均显著与未处理组相比干扰。此外，维持甲基化基因dnmt1在BPA暴露后的发育早期单调且显着降低，但相对于对照组，BPS治疗保持不变。DNMT3a和DNMT3b直系同源物在BPA / BPS胚胎暴露后发生明显变化。我们的数据表明，胚胎暴露于低浓度的BPA / BPS可能会损害斑马鱼早期发育中胰腺相关基因的正常表达和所选基因的DNA甲基化模式。