Mechanisms of hexabromocyclododecanes induced developmental toxicity in marine medaka (Oryzias melastigma) embryos

Abstract

Hexabromocyclododecanes (HBCDs) are widely used as additive brominated flame retardants, and are now ubiquitous contaminants in the environmental media and biota, including the marine environment and marine organisms. However, the impacts of HBCDs on marine fish are not well known. In this study the embryos of marine medaka (Oryzias melastigma) were used to assess the developmental toxicity of HBCDs. Freshly fertilized marine medaka embryos were exposed to various concentrations of technical HBCD (tHBCD, 0, 5, 20 and 50μg/L) until the first fry stage, and hatch success, morphology and cardiac function were examined. In all the exposure groups (5, 20 and 50μg/L) tHBCD significantly increased the embryo heart beats. The measurement of sinus venosus-bulbus arteriosus (SV-BA) distance indicated that tHBCD significantly enlarged the SV-BA distance at exposure concentrations of 20 and 50μg/L. The malformation rate at the first fry stage was also induced by tHBCD in a dose dependent manner, with the formation of pericardial edema and yolk sac edema as the most frequently observed malformation. In addition, the concentrations of total HBCD isomers (ΣHBCDs) in embryos in the current study were comparative with environmental levels and increased with increasing exposure duration. Furthermore, exposure to tHBCD also induced the level of 8-oxodG, a representative oxidative DNA damage. The mechanisms of HBCD-induced developmental toxicity were further explored by TUNEL assay, gel-based quantitative proteomic approach and measurement of the expression of several stress responsive genes, such as p53, TNF-α, IL-1β, CYP1A, COX-1 and COX-2, together with the activities of caspases. The results suggested that HBCDs exposure at environmentally realistic concentrations induced oxidative stress and apoptosis, and suppressed nucleotide and protein synthesis, which all together resulted in developmental toxicity, particularly in the cardiovascular system, in the embryos of O. melastigma.

Keywords: Developmental toxicity; Hexabromocyclododecanes; Oryzias melastigma; Oxidative stress.