Developmental Toxicology Branch, Toxicity Assessment Division (MD-67), National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711, United States.
Developmental Toxicology Branch, Toxicity Assessment Division (MD-67), National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711, United States.
Reprod Toxicol. 2012 Jul;33(4):491-505. doi: 10.1016/j.reprotox.2011.11.005. Epub 2011 Dec 1.
PPARs regulate metabolism and can be activated by environmental contaminants such as perfluorooctanoic acid (PFOA). PFOA induces neonatal mortality, developmental delay, and growth deficits in mice. Studies in genetically altered mice showed that PPARα is required for PFOA-induced developmental toxicity. In this study, pregnant CD-1 mice were dosed orally from GD1 to 17 with water or 5mg PFOA/kg to examine PPARα, PPARβ, and PPARγ expression and profile the effects of PFOA on PPAR-regulated genes. Prenatal and postnatal liver, heart, adrenal, kidney, intestine, stomach, lung, spleen, and thymus were collected at various developmental ages. RNA and protein were examined using qPCR and Western blot analysis. PPAR expression varied with age in all tissues, and in liver PPARα and PPARγ expression correlated with nutritional changes as the pups matured. As early as GD14, PFOA affected expression of genes involved in lipid and glucose homeostatic control. The metabolic disruption produced by PFOA may contribute to poor postnatal survival and persistent weight deficits of CD-1 mouse neonates.
过氧化物酶体增殖物激活受体（PPARs）可调节代谢，其活性可被全氟辛酸（PFOA）等环境污染物所激活。PFOA 可导致新生鼠死亡、发育迟缓及生长缺陷。基因改变的实验鼠研究显示，PPARα 是 PFOA 诱导发育毒性所必需的。本研究中，CD-1 孕鼠从 GD1 至 17 天经口给予水或 5mg PFOA/kg，以观察 PPARα、PPARβ 和 PPARγ 的表达，并分析 PFOA 对 PPAR 调控基因的影响。在不同发育阶段收集孕鼠和仔鼠的肝、心、肾上腺、肾、肠、胃、肺、脾和胸腺。采用 qPCR 和 Western blot 分析检测 RNA 和蛋白。PPAR 在所有组织中的表达均随年龄而变化，在肝中，PPARα 和 PPARγ 的表达与幼鼠成熟过程中营养变化相关。早在 GD14，PFOA 就影响了参与脂质和葡萄糖稳态控制的基因的表达。PFOA 引起的代谢紊乱可能导致 CD-1 新生鼠出生后存活率低和体重持续不足。
