环境剂量TDCIPP多代暴露对斑马鱼生长和生殖的影响及作用机制

As a class of replacements for the commercial PentaBDE mixture, Tris (1,3-dichloro-2-propyl) phosphate (TDCIPP) has been frequently detected in foam used in furniture and baby products, and thus humans are the most likely to be chronic exposed. Our previous study have demonstrated that exposure to environmentally relevant concentrations of TDCIPP caused inhibition of growth and reproductive impairs in zebrafish. However, the possible mechanisms of these actions of TDCIPP remain unclear. In addition, as the biota are exposed to TDCIPP for multiple generations in the natural ecosystem, it is essential to consider multigenerational testing to highlight the biological impacts over multiple generations. In our study, zebrafish embryos will be exposed to environmental relevant concentrations of TDCIPP over a three-generation exposure (F0, F1, and F2), and the effects of multigenerational exposure to TDCIPP at environmental relevant levels on zebrafish growth and reproduction will be evaluated. By using gene- , protein-, hormone-and histology -related methods, we will measure the effects of TDCIPP on growth related axis (hypothalamic–pituitary–thyroid (HPT) axis and growth hormone/ insulin-like growth factor (GH/IGF) axis) and reproductive related axis (hypothalamic–pituitary–gonad (HPG) axis) and explore the molecular toxicological mechanisms. This study will provide the information for ecotoxicity of TDCIPP and scientific basis for decision-making on environmental protection.

磷酸三（1,3-二氯异丙基）酯（tris(1,3-dichloro-2-propyl) phosphate, TDCIPP）作为多溴联苯醚（PBDEs）的主要替代品之一，大量存在于软垫家具和婴儿产品中，导致人群长期处于其慢性暴露环境中。我们前期研究发现低剂量 TDCIPP 长期暴露会抑制斑马鱼的生长，并对生殖产生影响，但其引起生长发育毒性和生殖毒性的机制目前尚不清楚。 在本研究中，将斑马鱼暴露于环境剂量的 TDCIPP 中并持续三代，研究 TDCIPP 多代暴露对每一代斑马鱼生长发育和生殖的影响。通过结合基因、蛋白、激素和组织学的研究方法，重点关注 TDCIPP 对生长发育相关轴（HPT 轴和 GH/IGF 轴）以及生殖相关轴（HPG）的影响，并试图阐明 TDCIPP 分子毒理学机制。本课题将为 TDCIPP 生态毒理学效应评价及环境保护决策提供科学依据。

磷酸三(1,3-二氯异丙基)酯(tris(1,3-dichloro-2-propyl) phosphate, TDCIPP)作为多溴联苯醚(PBDEs)的主要替代品之一，大量存在于软垫家具和婴儿产品中， 导致人群长期处于其慢性暴露环境中。本课题以斑马鱼为研究模型, 首先进行了环境剂量TDCIPP三代暴露实验，评价了TDCIPP对每一代斑马鱼生殖的影响。研究发现环境剂量TDCIPP暴露导致的生殖毒性以及神经发育毒性会随着暴露代数的增加而减弱，表现为F0代和F1代产卵量显著性下降，血浆中性激素水平紊乱，但F2代产卵量及其子代F3胚胎的受精率和存活率均不受影响。结合化学分析发现这可能与斑马鱼体内蓄积的TDCIPP量减少相关。我们也发现环境浓度TDCIPP长期暴露导致雌鱼生长抑制，而生长抑制可能与斑马鱼雌鱼的肠道受损，雌鱼肠道中的致病菌增多相关。母源性环境浓度TDCIPP暴露会导致子代仔鱼甲基化，引起神经细胞体相关基因启动子区域甲基化差异变化，基因表达改变，导致仔鱼运动行为发生显著变化。上述研究结果发表在环境毒理学国际核心杂志Environmental pollution (2篇) 、Chemosphere(1篇) Aquatic toxicology （1篇），中文核心期刊《生态毒理学报》（1篇）上，为全面评价TDCIPP的生态健康风险提供理论依据，并为其他有机磷阻燃剂污染物的毒性评价提供新的思路。