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Maternal exposure to a human based mixture of persistent organic pollutants (POPs) affect gene expression related to brain function in mice offspring hippocampus
Chemosphere ( IF 8.8 ) Pub Date : 2021-03-03 , DOI: 10.1016/j.chemosphere.2021.130123
Oddvar Myhre , Karin E. Zimmer , Alexandra M. Hudecova , Kristine E.A. Hansen , Abdolrahman Khezri , Hanne F. Berntsen , Vidar Berg , Jan L. Lyche , Siddhartha Mandal , Nur Duale , Erik Ropstad

Male and female mice pups were exposed to a low and high dose of a human relevant mixture of persistent organic pollutants (POPs) during pregnancy and lactation. Most compounds detected in the dams were found in offspring brains. The mice offspring exhibited changed expression of hippocampal genes involved in cognitive function (Adora2a, Auts2, Crlf1, Chrnb2, Gdnf, Gnal, Kcnh3), neuroinflammation (Cd47, Il1a), circadian rhythm (Per1, Clock), redox signalling (Hmox2) and aryl hydrocarbon receptor activation (Cyp1b1). A few genes were differentially expressed in males versus females. Mostly, similar patterns of gene expression changes were observed between the low and high dose groups. Effects on learning and memory function measured in the Barnes maze (not moving, escape latency) were found in the high dose group when combined with moderate stress exposure (air flow from a fan). Mediation analysis indicated adaptation to the effects of exposure since gene expression compensated for learning disabilities (escape latency, walking distance and time spent not moving in the maze). Additionally, random forest analysis indicated that Kcnh3, Gnal, and Crlf1 were the most important genes for escape latency, while Hip1, Gnal and the low exposure level were the most important explanatory factors for passive behaviour (not moving). Altogether, this study showed transfer of POPs to the offspring brains after maternal exposure, modulating the expression level of genes involved in brain function.



中文翻译:

孕妇暴露于人为基础的持久性有机污染物(POPs)混合物会影响小鼠后代海马体中与脑功能相关的基因表达

雄性和雌性幼崽在怀孕和哺乳期间均暴露于低剂量和高剂量的人类相关性持久性有机污染物(POPs)混合物中。在大坝中检测到的大多数化合物都是在后代大脑中发现的。小鼠后代表现出改变的表达参与认知功能(海马基因ADORA2AAUTS2,CRLF1Chrnb2的GDNFGnal,Kcnh3),神经炎症(CD47IL1A),昼夜节律(PER1时钟),氧化还原信号(Hmox2)和芳烃受体激活(Cyp1b1)。一些基因在男性和女性中差异表达。通常,在低剂量组和高剂量组之间观察到相似的基因表达变化模式。当与中等压力暴露(来自风扇的气流)结合使用时,在高剂量组中发现了在Barnes迷宫中测量的对学习和记忆功能的影响(不移动,逃避潜伏期)。调解分析表明适应了暴露的影响,因为基因表达弥补了学习障碍(逃生潜伏期,步行距离和在迷宫中不移动所花费的时间)。此外,随机森林分析表明Kcnh3GnalCrlf1是逃避潜伏期最重要的基因,而Hip1Gnal和低暴露水平是导致被动行为(不动)的最重要的解释因素。总而言之,这项研究表明,POPs在母体接触后会转移到后代大脑,从而调节参与大脑功能的基因的表达水平。

更新日期:2021-03-11
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