Waterborne exposure to low concentrations of BDE-47 impedes early vascular development in zebrafish embryos/larvae

Abstract

Polybrominated diphenyl ethers (PBDEs) are persistent flame retardants ubiquitously existing in various environment matrices. In spite of a recent reduction in use according to the phase-out policy, high levels of PBDEs are still found in both environmental and biological samples due to their persistent property and large-scale production over a long history. Developmental toxicity is a major health concern of PBDEs. However, the impact of PBDE exposure on vascular development remains poorly understood. In this study, we investigated the effect of low concentrations of 2,2′,4,4′-Tetrabromodiphenyl ether (BDE-47), a predominant PBDE congener, in environmental matrices and biota, on early vascular development using zebrafish. Zebrafish embryos were continuously exposed to waterborne BDE-47 at 0.06, 0.2, 0.6 μM starting from 2 h post-fertilization (hpf). Fluorescent images of vasculatures in Tg(kdrl:eGFP) zebrafish were acquired using a confocal microscope. The results indicated that BDE-47 exposure had no effect on hatching rate, survival, body weight, body length or heart rate in the early stage within 72 hpf, whereas zebrafish exposed to BDE-47 exhibited impairments in the growth of multiple types of blood vessels. The percentage of completed intersegmental vessels (ISV) at 30 hpf decreased in embryos treated with BDE-47 in a dose-dependent fashion. BDE-47 exposure led to a slight decrease in the growth of common cardinal vein (CCV), while dramatically hindered CCV remodeling process reflected by the larger CCV area and wider ventral diameter. BDE-47 exposure significantly reduced sub-intestinal vessels (SIV) area as well as the vascularized yolk area in zebrafish larvae at 72 hpf. In addition, the expression of genes related to vascular growth and remodeling was markedly suppressed in BDE-47-exposed zebrafish. These findings demonstrate the adverse effects of BDE-47 on early vascular development, and confirm the vascular toxicity of PBDEs in vivo. The results indicate that developing vasculature in zebrafish is sensitive to BDE-47 exposure, and may serve as a powerful tool for the assessment of early exposure to PBDEs.