Effects of perfluorooctanoic acid (PFOA) on expression of peroxisome proliferator-activated receptors (PPAR) and nuclear receptor-regulated genes in fetal and postnatal CD-1 mouse tissues
Effects of perfluorooctanoic acid (PFOA) on expression of peroxisome proliferator-activated receptors (PPAR) and nuclear receptor-regulated genes in fetal and postnatal CD-1 mouse tissues
复制标题
DOI：
10.1016/j.reprotox.2011.11.005
复制
发表时间：
2012-07-01
影响因子：
3.3
通讯作者：
Lau, Christopher
中科院分区：
文献类型：
--
作者：
Abbott, Barbara D.;Wood, Carmen R.;Lau, Christopher
PPARs调节新陈代谢，并可被环境污染物如全氟辛酸（PFOA）激活。PFOA可诱导小鼠新生儿死亡、发育迟缓和生长缺陷。对转基因小鼠的研究表明，PFOA诱导的发育毒性需要PPAR α。在这项研究中，妊娠CD-1小鼠从GD 1至17口服水或5 mg PFOA/kg，以检查PPAR α、PPAR β和PPAR γ表达，并分析PFOA对PPAR调节基因的影响。在不同发育年龄采集出生前和出生后肝脏、心脏、肾上腺、肾脏、肠、胃、肺、脾和胸腺。使用qPCR和Western印迹分析检测RNA和蛋白质。在所有组织中，过氧化物酶体增殖物激活受体的表达随年龄而变化，肝脏中的过氧化物酶体增殖物激活受体α和过氧化物酶体增殖物激活受体γ的表达与幼鼠成熟时的营养变化相关。早在GD 14。PFOA影响参与脂质和葡萄糖稳态控制的基因表达。PFOA引起的代谢紊乱可能导致CD-1小鼠新生儿出生后存活率差和持续体重不足。爱思唯尔公司出版
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 PPAR alpha is required for PFOA-induced developmental toxicity. In this study, pregnant CD-1 mice were dosed orally from GD1 to 17 with water or 5 mg PFOA/kg to examine PPAR alpha, PPAR beta, and PPAR gamma 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 PPAR alpha and PPAR gamma 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. Published by Elsevier Inc.