GENE EXPRESSION EFFECT OF EARLY DEVELOPMENTAL EXPOSURES TO BISPHENOL A AND ITS ALTERNATIVES ON THE REPRODUCTIVE REGULATORY AXIS

Bisphenol A (BPA) is a known endocrine-disrupting chemical (EDC) and also a food safety concern due to leaching of BPA from food and beverage containers into the foodstuff. Substitutes such as BPB, BPAF, BPAP, BPS and BPZ were developed but there is still concern over their toxicity due to their structural similarity to BPA. The objective of this study is to perform direct comparison of six bisphenol analogues to BPA and control on their effects on the gene expression of the hypothalamic-pituitary-gonadal (HPG) axis in the early developmental phase. Acute toxicity and gene expression studies were performed using early developmental-stage zebrafish larvae. Additionally, literature review was performed to further understand the result of our toxicity exposure study. Our study found BPAF to be the most and BPF and BPS as the least toxic in terms of lethality. However, only one gene (lhb) was significantly induced by BPAF at below sublethal doses, while three genes (vtg1, lhb and gnrh3) were induced by both BPF and BPS. The extent of induction of arom-b and vtg1 in the complex mixture group cannot simply be explained by an additive effect of 7 bisphenols and may indicate a significant synergistic effect occur with combined exposures. The result for BPS and BPF was consistent with data from literature, although there were some inconsistencies with BPAF effects. In conclusion, our study indicated that while BPS were found to be less toxic compared to BPA in terms of lethality, they may still trigger endocrine- disrupting activity, especially when it exists in complex mixtures, which is demonstrated by their effect on the gene expression of reproductively relevant genes on the HPG axi