Pharmacology & Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40536, USA.
Nutrition and Health Sciences, Laney Graduate School, Emory University, Atlanta, GA 30322, USA; Medical Scientist Training Program, Emory University School of Medicine, Atlanta, GA 30322, USA.
Reprod Toxicol. 2023 Aug;119:108385. doi: 10.1016/j.reprotox.2023.108385. Epub 2023 Apr 18.
Polychlorinated biphenyls (PCBs) are organic pollutants that can have lasting impacts on offspring health. Here, we sought to examine maternal and fetal gene expression differences of aryl hydrocarbon receptor (AHR)-regulated genes in a mouse model of prenatal PCB126 exposure. Female mice were bred and gavaged with 1 µmole/kg bodyweight PCB126 or vehicle control on embryonic days 0 and 14, and maternal and fetal tissues were collected on embryonic day 18.5. Total RNAs were isolated, and gene expression levels were analyzed in both maternal and fetal tissues using the NanoString nCounter system. Interestingly, we found that the expression levels of cytochrome P450 (Cyp)1a1 and Cyp1b1 were significantly increased in response to PCB exposure in the tested maternal and fetal tissues. Furthermore, PCB exposure altered the expression of several other genes related to energy balance, oxidative stress, and epigenetic regulation in a manner that was less consistent across tissue types. These results indicate that maternal PCB126 exposure significantly alters gene expression in both developing fetuses and pregnant dams, and such changes vary in intensity and expressivity depending on tissue type. The altered gene expression may provide insights into pathophysiological mechanisms by which in utero PCB exposures contribute to PCB-induced postnatal metabolic diseases.
多氯联苯 (PCBs) 是一种有机污染物,会对后代健康产生持久影响。在这里,我们试图在产前 PCB126 暴露的小鼠模型中检查母体和胎儿芳烃受体 (AHR) 调节基因的基因表达差异。雌性小鼠在胚胎第 0 天和第 14 天接受 1 µmole/kg 体重的 PCB126 或载体对照的灌胃,并在胚胎第 18.5 天收集母体和胎儿组织。提取总 RNA,并使用 NanoString nCounter 系统分析母体和胎儿组织中的基因表达水平。有趣的是,我们发现,在测试的母体和胎儿组织中,Cyp1a1 和 Cyp1b1 的表达水平因 PCB 暴露而显著增加。此外,PCB 暴露以组织类型之间一致性较差的方式改变了与能量平衡、氧化应激和表观遗传调节相关的几个其他基因的表达。这些结果表明,母体 PCB126 暴露显著改变了发育中胎儿和怀孕母体的基因表达,并且这种变化的强度和表达因组织类型而异。改变的基因表达可能为 PCB 暴露导致出生后代谢疾病的病理生理机制提供了见解。