Embryonic Exposure to Low Concentrations of Bisphenol A and S Altered Genes Related to Pancreaticβ-Cell Development and DNA Methyltransferase in Zebrafish.
Arch Environ Contam Toxicol. 2021 Feb ;80(2):450-460. Epub 2021 Jan 20. PMID: 33471154
Bisphenol A (BPA) and bisphenol S (BPS) are implicated in the development of metabolic disorders, such diabetes mellitus. However, the epigenetic mechanism underlying the pancreaticβ-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.