Section of Toxicology and Risk Assessment, Norwegian Institute of Public Health, P. O. Box 222 Skøyen, N-0213, Oslo, Norway.
Department of Preclinical Sciences and Pathology, Physiology Unit, Faculty of Veterinary Medicine, Norwegian University of Life Sciences, P. O. Box 5003, 1433 Ås, Norway.
Chemosphere. 2021 Aug;276:130123. doi: 10.1016/j.chemosphere.2021.130123. Epub 2021 Mar 3.
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.
雄性和雌性幼鼠在孕期和哺乳期暴露于低剂量和高剂量的人类相关持久性有机污染物（POPs）混合物中。在母体中检测到的大多数化合物都存在于后代的大脑中。这些幼鼠后代表现出海马体中与认知功能（Adora2a、Auts2、Crlf1、Chrnb2、Gdnf、Gnal、Kcnh3）、神经炎症（Cd47、Il1a）、昼夜节律（Per1、Clock）、氧化还原信号（Hmox2）和芳香烃受体激活（Cyp1b1）相关的基因表达发生改变。少数基因在雄性和雌性之间存在差异表达。大多数情况下，低剂量和高剂量组之间观察到相似的基因表达变化模式。在 Barnes 迷宫（无移动、逃逸潜伏期）中测量的学习和记忆功能的影响仅在高剂量组与中度应激暴露（风扇产生的气流）相结合时才会出现。中介分析表明，由于基因表达代偿了学习障碍，因此适应了暴露的影响（逃逸潜伏期、行走距离和在迷宫中不移动的时间）。此外，随机森林分析表明，Kcnh3、Gnal 和 Crlf1 是逃逸潜伏期最重要的基因，而 Hip1、Gnal 和低暴露水平是被动行为（不移动）最重要的解释因素。总的来说，这项研究表明，母体暴露后 POPs 会转移到后代的大脑中，调节与大脑功能相关的基因的表达水平。
