Sun Guijin, Liu Kechun
School of Food Science and Engineering, Qilu University of Technology, Jinan 250014, China.
Biology Institute, Shandong Academy of Sciences, Jinan 250014, China.
Aquat Toxicol. 2017 Nov;192:165-170. doi: 10.1016/j.aquatox.2017.09.020. Epub 2017 Sep 22.
Phthalic acid esters (PAEs), commonly called phthalates, have become ubiquitous environment pollutants. Studies have focused on reproductive toxicity, neurotoxicity, teratogenicity, tumourigenesis, and mutagenesis of phthalates. However, relatively little is known about the phthalates effects on the heart. Butyl benzyl phthalate (BBP), a member of PAEs, is classified by the US Environmental Protection Agency as a priority environmental pollutant. We studied the developmental toxicity of BBP, especially its effects on the heart development, in zebrafish (Danio rerio) embryos. Embryos at 4hr post-fertilization (hpf) were exposed to 0, 0.1, 0.6 and 1.2mg/L BBP until 72hpf. BBP caused abnormalities in embryo morphology, including yolk-sac edema, spinal curvature, tail deformity, uninflated swim bladder and cardiac defects. Exposure to 0.6mg/L BBP significantly increased the malformation rate, caused growth inhibition, increased the cardiac malformation rate as well as the distance between the sinus venosus (SV) and bulbus arteriosus (BA), and reduced the heart rate of embryos. Exposure to 1.2mg/L BBP significantly affected all endpoints, except survival rate at 24hpf. To preliminarily elucidate the potential mechanism of heart developmental toxicity caused by BBP, we examined the expression of two genes related to heart development, Nkx2.5 and T-box transcription factor 5, by real-time quantitative PCR. The expression of the two genes was dose-dependently downregulated with BBP. BBP could induce developmental toxicity, with adverse effects on the heart development in zebrafish embryos, and alter the expression of genes related to heart development.
邻苯二甲酸酯(PAEs),通常称为邻苯二甲酸盐,已成为普遍存在的环境污染物。研究主要集中在邻苯二甲酸盐的生殖毒性、神经毒性、致畸性、肿瘤发生和致突变性。然而,关于邻苯二甲酸盐对心脏的影响相对知之甚少。邻苯二甲酸丁苄酯(BBP)是PAEs的一种,被美国环境保护局列为优先环境污染物。我们研究了BBP在斑马鱼(Danio rerio)胚胎中的发育毒性,特别是其对心脏发育的影响。受精后4小时(hpf)的胚胎暴露于0、0.1、0.6和1.2mg/L的BBP中,直至72hpf。BBP导致胚胎形态异常,包括卵黄囊水肿、脊柱弯曲、尾巴畸形、鳔未充气和心脏缺陷。暴露于0.6mg/L的BBP显著增加了畸形率,导致生长抑制,增加了心脏畸形率以及静脉窦(SV)和动脉球(BA)之间的距离,并降低了胚胎的心率。暴露于1.2mg/L的BBP显著影响了所有终点指标,但24hpf时的存活率除外。为了初步阐明BBP导致心脏发育毒性的潜在机制,我们通过实时定量PCR检测了两个与心脏发育相关的基因Nkx2.5和T-box转录因子5的表达。这两个基因的表达随BBP剂量依赖性下调。BBP可诱导发育毒性,对斑马鱼胚胎心脏发育产生不利影响,并改变与心脏发育相关的基因表达。