Embryonic Exposure to Low Concentrations of Bisphenol A and S Altered Genes Related to Pancreatic β-Cell Development and DNA Methyltransferase in Zebrafish.

Abstract

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 1.0µM 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 1.0µM BPA, while 0.32 and 0.24-fold of insulin expression were elicited by 0.3 and 1µM BPS respectively at 72 hpf. Significant elevation of glucose levels; 16.3% (for 1.0µM BPA), 7.20% (for 0.3µM BPS), and 74.09% (for 1.0µM 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.