Lin Han, Yuan Kaiming, Li Linyan, Liu Shiwen, Li Senlin, Hu Guoxin, Lian Qing-Quan, Ge Ren-Shan
Department of Anesthesiology, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, China.
Int J Environ Res Public Health. 2015 Oct 28;12(11):13696-710. doi: 10.3390/ijerph121113696.
Diethylhexyl phthalate (DEHP) is one of the most widely utilized phthalate plasticizers. Previous studies have demonstrated that gestational or postnatal DEHP exposure induced adverse effects on rat brain development and function. In this study, we investigated the effects of gestational DEHP exposure on gene expression profiling in neonatal rat brain and cognitive function change at adulthood. Adult Sprague Dawley dams were orally treated with 10 or 750 mg/kg DEHP from gestational day 12 to 21. Some male pups were euthanized at postnatal day 1 for gene expression profiling, and the rest males were retained for water maze testing on postnatal day (PND) 56. DEHP showed dose-dependent impairment of learning and spatial memory from PND 56 to 63. Genome-wide microarray analysis showed that 10 and 750 mg/kg DEHP altered the gene expression in the neonatal rat brain. Ccnd1 and Cdc2, two critical genes for neuron proliferation, were significantly down-regulated by DEHP. Interestingly, 750 mg/kg DEHP significantly increased Pmch level. Our study demonstrated the changed gene expression patterns after in utero DEHP exposure might partially contribute to the deficit of cognitive function at adulthood.
邻苯二甲酸二（2-乙基己基）酯（DEHP）是使用最广泛的邻苯二甲酸酯类增塑剂之一。先前的研究表明，孕期或产后暴露于DEHP会对大鼠脑发育和功能产生不良影响。在本研究中，我们调查了孕期暴露于DEHP对新生大鼠脑内基因表达谱以及成年后认知功能变化的影响。成年斯普拉格-道利母鼠在妊娠第12天至21天经口给予10或750 mg/kg的DEHP。一些雄性幼崽在出生后第1天安乐死以进行基因表达谱分析，其余雄性幼崽留作在出生后第56天进行水迷宫测试。从出生后第56天至63天，DEHP对学习和空间记忆的损害呈剂量依赖性。全基因组微阵列分析表明，10和750 mg/kg的DEHP改变了新生大鼠脑内的基因表达。Ccnd1和Cdc2这两个神经元增殖的关键基因被DEHP显著下调。有趣的是，750 mg/kg的DEHP显著提高了Pmch水平。我们的研究表明，子宫内暴露于DEHP后基因表达模式的改变可能部分导致成年后认知功能的缺陷。
