Abstract：
6:2 fluorotelomer carboxylic acid (6:2 FTCA) is a perfluorooctanoic acid (PFOA) substitute, which is supposedly less accumulative and toxic than PFOA. However, 6:2 FTCA is structurally similar to PFOA, and there had already been reports about its toxicities comparable to PFOA. The aim of the current study is to assess potential effects of developmental exposure to 6:2 FTCA on the development of kidney in chicken embryo and to investigate underlying mechanism. Fertile chicken eggs were exposed to 1.25 mg/kg, 2.5 mg/kg or 5 mg/kg doses of 6:2 FTCA, or 2 mg/kg PFOA, then incubated to hatch. Serum and kidney of hatchling chickens were collected. Blood urea nitrogen (BUN) and creatinine (Cre) levels were measured with commercially available kits. Morphology of kidney was assessed with histopathology. To further reveal molecular mechanism of observed endpoints, IGF signaling molecules were assessed in the kidney samples with qRT-PCR, results indicated that IGFBP3 is a potentially crucial molecule. Lentiviruses overexpressing or silencing IGFBP3 were designed and applied to enhance/suppress the expression of IGFBP3 in developing chicken embryo for further verification of its role in the observed effects. Disrupted nephron formation, in the manifestation of decreased glomeruli number/area and increased serum BUN/Cre levels, was observed in the animals developmentally exposed to 6:2 FTCA. Correspondingly, IGF signaling molecules (IGF1, IGF1R and IGFBP3) were affected by 6:2 FTCA exposure. Meanwhile, overexpression of IGFBP3 effectively alleviated such changes, while silencing of IGFBP3 mimicked observed effects. In conclusion, developmental exposure to 6:2 FTCA is associated with disrupted chicken embryo renal development, in which IGFBP3 seems to be a remarkable contributor, suggesting potential health risks for human and other species. Further risk assessments and mechanistic works are necessary.
摘要：
6：2氟调聚物羧酸（6：2FTCA）是全氟辛酸（PFOA）替代品，据说比PFOA更少积累和毒性。然而,6:2FTCA在结构上与PFOA相似，并且已经有关于其毒性与PFOA相当的报道。本研究的目的是评估发育暴露于6：2FTCA对鸡胚肾脏发育的潜在影响，并探讨其潜在机制。肥沃的鸡蛋暴露于1.25毫克/千克，2.5mg/kg或5mg/kg剂量的6:2FTCA，或2mg/kgPFOA，然后孵化。收集孵化鸡的血清和肾脏。用市售试剂盒测量血尿素氮(BUN)和肌酸酐(Cre)水平。用组织病理学评估肾脏的形态。为了进一步揭示观察到的端点的分子机制，使用qRT-PCR评估肾脏样品中的IGF信号分子，结果表明IGFBP3是一个潜在的关键分子。设计过表达或沉默IGFBP3的慢病毒并应用于在发育中的鸡胚中增强/抑制IGFBP3的表达,以进一步验证其在观察到的效果中的作用。肾单位形成中断,在肾小球数量/面积减少和血清BUN/Cre水平增加的表现中，在发育中暴露于6:2FTCA的动物中观察到。相应地,IGF信号分子(IGF1、IGF1R和IGFBP3)受到6:2FTCA暴露的影响。同时,IGFBP3的过表达有效缓解了这种变化，而IGFBP3的沉默模拟了观察到的效果。总之,发育暴露于6：2FTCA与鸡胚肾脏发育中断有关，IGFBP3似乎是一个非凡的贡献者，提示人类和其他物种的潜在健康风险。进一步的风险评估和机械工作是必要的。
