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胚胎期暴露于过氧化物酶体增殖物激活受体α(PPARα)激动剂 GW7647 或全氟辛烷磺酸(PFOS)或全氟辛酸(PFOA)的鸡胚中参与脂肪代谢的基因转录。

Transcription of genes involved in fat metabolism in chicken embryos exposed to the peroxisome proliferator-activated receptor alpha (PPARα) agonist GW7647 or to perfluorooctane sulfonate (PFOS) or perfluorooctanoic acid (PFOA).

机构信息

Department of Environmental Toxicology, Uppsala University, Sweden.

出版信息

Comp Biochem Physiol C Toxicol Pharmacol. 2012 Jun;156(1):29-36. doi: 10.1016/j.cbpc.2012.03.004. Epub 2012 Mar 21.

DOI:10.1016/j.cbpc.2012.03.004
PMID:22465071
Abstract

Perfluoroalkyl acids (PFAAs) such as perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are developmental toxicants in various animal classes, including birds. Both compounds interact with peroxisome proliferator-activated receptors (PPARs), but it is not known whether activation of PPARs is involved in their embryo toxicity in birds. We exposed chicken embryos via egg injection at a late developmental stage to GW7647, a potent PPARα agonist in mammals, and to PFOS or PFOA. Mortality was induced by PFOS and PFOA but not by GW7647. Transcripts of a number of genes activated by PPARα agonists in mammals were analyzed in liver and kidney of 18-day-old embryos. Several of the genes were induced in both liver and kidney following exposure to GW7647. Treatment with PFOA resulted in induction of acyl-coenzyme A oxidase mRNA in liver, whereas none of the genes were significantly induced by PFOS treatment. No up-regulation of gene transcription was found in kidney following treatment with PFOS or PFOA. Principal component analysis showed that PFOA caused an mRNA expression pattern in liver more similar to the pattern induced by GW7647 than PFOS did. Our findings do not support that the embryo mortality by PFOS and PFOA in chicken embryos involves PPARα activation.

摘要

全氟烷基酸(PFAAs),如全氟辛烷磺酸(PFOS)和全氟辛酸(PFOA),是各种动物类群(包括鸟类)的发育毒物。这两种化合物都与过氧化物酶体增殖物激活受体(PPARs)相互作用,但尚不清楚激活 PPAR 是否参与它们在鸟类中的胚胎毒性。我们通过蛋内注射在晚期发育阶段将 GW7647(哺乳动物中一种有效的 PPARα 激动剂)、PFOS 或 PFOA 暴露于鸡胚胎中。PFOS 和 PFOA 诱导了死亡率,但 GW7647 没有。分析了 18 日龄胚胎肝脏和肾脏中哺乳动物中 PPARα 激动剂激活的许多基因的转录物。几种基因在暴露于 GW7647 后在肝脏和肾脏中均被诱导。PFOA 处理导致肝脏中酰基辅酶 A 氧化酶 mRNA 的诱导,而 PFOS 处理则没有显著诱导任何基因。PFOS 或 PFOA 处理后,在肾脏中未发现基因转录的上调。主成分分析表明,PFOA 在肝脏中引起的 mRNA 表达模式与 GW7647 诱导的模式更相似,而不是 PFOS。我们的研究结果不支持 PFOS 和 PFOA 在鸡胚胎中引起胚胎死亡率涉及 PPARα 激活。

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