Embryonic exposure to tetrabromobisphenol A and its metabolites, bisphenol A and tetrabromobisphenol A dimethyl ether disrupts normal zebrafish ( Danio rerio) development and matrix metalloproteinase expression

Abstract

Tetrabromobisphenol A (TBBPA) is a widely used brominated flame retardant that is persistent in the environment and detected in human serum and breast milk. TBBPA is microbiologically transformed in anaerobic environments to bisphenol A (BPA) and in aerobic environments to TBBPA dimethyl ether (TBBPA DME). Despite the detection of TBBPA DME in the environment, the resulting toxicity is not known. The relative toxicity of TBBPA, BPA and TBBPA DME was determined using embryonic exposure of zebrafish, with BPA and TBBPA DME exhibiting lower potency than TBBPA. TBBPA exposure resulted in 100% mortality at 3 (1.6 mg/L) and 1.5 μM (0.8 mg/L), whereas BPA and TBBPA DME did not result in significant embryonic mortality in comparison to controls. While all three caused edema and hemorrhage, only TBBPA specifically caused decreased heart rate, edema of the trunk, and tail malformations. Matrix metalloproteinase (MMP) expression was measured due to the role of these enzymes in the remodeling of the extracellular matrix during tissue morphogenesis, wound healing and cell migration. MMP-2, -9 and -13 expression increased (2–8-fold) after TBBPA exposure followed by an increase in the degradation of collagen I and gelatin. TBBPA DME exposure resulted in only a slight increase (less than 2-fold) in MMP expression and did not significantly increase enzymatic activity. These data suggest that TBBPA is more potent than BPA or TBBPA DME and indicate that the trunk and tail phenotypes seen after TBBPA exposure could be due in part to alteration of proper MMP expression and activity.