Department of Environmental Sciences, University of California, Riverside, CA 92521, United States.
Division of Environmental Sciences and Policy, Duke University, Durham, NC 27708, United States.
Environ Int. 2023 Feb;172:107757. doi: 10.1016/j.envint.2023.107757. Epub 2023 Jan 16.
Pericardial edema is commonly observed in zebrafish embryo-based chemical toxicity screens, and a mechanism underlying edema may be disruption of embryonic osmoregulation. Therefore, the objective of this study was to identify whether triphenyl phosphate (TPHP) - a widely used aryl phosphate ester-based flame retardant - induces pericardial edema via impacts on osmoregulation within embryonic zebrafish. In addition to an increase in TPHP-induced microridges in the embryonic yolk sac epithelium, an increase in ionic strength of exposure media exacerbated TPHP-induced pericardial edema when embryos were exposed from 24 to 72 h post-fertilization (hpf). However, there was no difference in embryonic sodium concentrations in situ within TPHP-exposed embryos relative to embryos exposed to vehicle (0.1% DMSO) from 24 to 72 hpf. Interestingly, increasing the osmolarity of exposure media with mannitol (an osmotic diuretic which mitigates TPHP-induced pericardial edema) and increasing the ionic strength of the exposure media (which exacerbates TPHP-induced pericardial edema) did not affect embryonic doses of TPHP, suggesting that TPHP uptake was not altered under these varying experimental conditions. Overall, our findings suggest that TPHP-induced pericardial edema within zebrafish embryos is dependent on the ionic strength of exposure media, underscoring the importance of further standardization of exposure media and embryo rearing protocols in zebrafish-based chemical toxicity screening assays.
心包水肿在基于斑马鱼胚胎的化学毒性筛选中较为常见，水肿的一种潜在机制可能是胚胎渗透压调节的破坏。因此，本研究的目的是确定是否三苯基磷酸酯（TPHP）——一种广泛使用的基于芳基磷酸酯的阻燃剂——通过对胚胎斑马鱼的渗透压调节产生影响而导致心包水肿。除了胚胎卵黄囊上皮细胞中的微脊数量因 TPHP 增加外，当胚胎在受精后 24 至 72 小时（hpf）期间暴露于暴露介质的离子强度增加时，也会加剧 TPHP 诱导的心包水肿。然而，与胚胎在 24 至 72 hpf 期间暴露于载体（0.1% DMSO）相比，暴露于 TPHP 的胚胎中胚胎内钠离子浓度原位无差异。有趣的是，用甘露醇（一种减轻 TPHP 诱导的心包水肿的渗透利尿剂）增加暴露介质的渗透压，以及增加暴露介质的离子强度（会加剧 TPHP 诱导的心包水肿），均不影响胚胎中 TPHP 的剂量，这表明在这些不同的实验条件下，TPHP 的摄取没有改变。总的来说，我们的研究结果表明，TPHP 诱导的斑马鱼胚胎心包水肿依赖于暴露介质的离子强度，这突显了在基于斑马鱼的化学毒性筛选试验中进一步标准化暴露介质和胚胎饲养方案的重要性。
