Chigusa Kaori, Kanda Kazuki, Iwata Hisato
Center for Marine Environmental Studies, Ehime University, Matsuyama 790-8577, Japan.
Center for Marine Environmental Studies, Ehime University, Matsuyama 790-8577, Japan.
Ecotoxicol Environ Saf. 2023 Oct 1;264:115445. doi: 10.1016/j.ecoenv.2023.115445. Epub 2023 Sep 13.
Tris(2-chloroisopropyl) phosphate (TCIPP) is an organophosphate flame retardant detected in the environment and eggs, feathers, and livers. Early-developmental-stage avian embryos are vulnerable to the toxic effects of chemicals. However, studies on the specific effects of TCIPP on avian embryonic development are limited. We aimed to investigate the toxicity of TCIPP in early chicken embryos using a previously developed shell-less incubation system. Fertilized chicken (Gallus gallus domesticus) eggs (n = 220) were exposed to 50 or 500 nmol TCIPP/(g egg) or dimethyl sulfoxide (DMSO) as a vehicle control on Day 0 of incubation. Development of 198 embryos was monitored from Days 3-9 of incubation, and 22 embryos on Day 4 and 74 embryos on Day 9 were dissected. Messenger RNA expression levels for several genes were measured in embryos on Day 4. Both TCIPP-exposed groups showed a significant reduction in survival rate. Imaging analyses revealed significant decreases in body length, head and bill length, eye diameter, and forelimb and hindlimb length in both TCIPP-treated groups. TCIPP exposure significantly impaired the development of extraembryonic blood vessels and the production of red blood cells. A TCIPP-dose-dependent decreasing trend in heart rate was observed on Days 4-7. The somitic angle increased significantly on Days 4-6, and embryos with curved somites showed cleavage in the back and gaps between somites, resulting in asymmetrical somite formation. A significant correlation was found between the somitic angle and FGF8 expression levels, suggesting that TCIPP exposure affects somite formation through an altered FGF-signaling pathway. Embryos with somitic deformities in TCIPP-exposed groups had significantly reduced survival rates, indicating that abnormal segment formation directly increased mortality. Finally, eye weight and ocular luminosity values were significantly reduced, suggesting that TCIPP may also affect eye development. Overall, these findings highlight severe toxic effects of TCIPP on avian embryonic development, including in vascularization, cardiac function, and somite and ocular development.
磷酸三（2-氯异丙基）酯（TCIPP）是一种在环境以及鸡蛋、羽毛和肝脏中被检测到的有机磷酸酯阻燃剂。鸟类胚胎的早期发育阶段易受化学物质毒性影响。然而，关于TCIPP对鸟类胚胎发育具体影响的研究有限。我们旨在使用先前开发的无壳孵化系统研究TCIPP对鸡早期胚胎的毒性。在孵化第0天，将受精的鸡（家鸡）蛋（n = 220）暴露于50或500 nmol TCIPP/（g蛋）或作为溶剂对照的二甲基亚砜（DMSO）中。在孵化第3 - 9天监测198个胚胎的发育情况，并在第4天解剖22个胚胎，在第9天解剖74个胚胎。在第4天测量胚胎中几个基因的信使核糖核酸表达水平。两个TCIPP暴露组的存活率均显著降低。成像分析显示，两个TCIPP处理组的体长、头和喙长度、眼直径以及前肢和后肢长度均显著减小。TCIPP暴露显著损害了胚外血管的发育和红细胞的产生。在第4 - 7天观察到心率呈TCIPP剂量依赖性下降趋势。在第4 - 6天，体节角显著增加，体节弯曲的胚胎背部出现裂开和体节间间隙，导致体节形成不对称。发现体节角与FGF8表达水平之间存在显著相关性，表明TCIPP暴露通过改变FGF信号通路影响体节形成。TCIPP暴露组中出现体节畸形的胚胎存活率显著降低，表明异常节段形成直接增加了死亡率。最后，眼重和眼亮度值显著降低，表明TCIPP可能也会影响眼睛发育。总体而言，这些发现突出了TCIPP对鸟类胚胎发育的严重毒性影响，包括血管生成、心脏功能以及体节和眼睛发育。
