College of Biotechnology and Bioengineering, Zhejiang University of Technology, 18, Chaowang Road, Hangzhou 310014, China.
Institute of Translational Medicine, Zhejiang Shuren University, Hangzhou 310015, China.
Chem Res Toxicol. 2022 Apr 18;35(4):651-662. doi: 10.1021/acs.chemrestox.1c00424. Epub 2022 Apr 4.
The toxicity of perfluorinated compounds (PFCs) to mammals has recently received increasing attention. However, the effects of maternal sodium -perfluorous nonenoxybenzene sulfonate (OBS) exposure during pregnancy and lactation on the liver function of dams (F0) and offspring (F1) mice are still unknown. The results demonstrated that maternal OBS treatment could not only induce lipid metabolism dysfunction but also disrupt amino acid metabolism in the liver of F0 and F1 generations. OBS had marked accumulation in the liver, and the serum and liver triglyceride (TG) levels increased in the F0 and F1 generations after maternal OBS exposure. Moreover, maternal OBS exposure changed the transcriptional levels of genes related to lipid metabolism (fatty acid (FA) synthesis, TG synthesis, and transport) and induced changes in the amino acid level in dams and 20-day-old mice offspring (F1-20 d). Additionally, the regulation of lipid metabolism by OBS was mainly dependent on the activation of peroxisome proliferator-activated receptor γ (PPARγ) and cluster of differentiation 36 (CD36). Interestingly, OBS could also disturb tyrosine (TYR) metabolism by increasing the TYR level and downregulating fumarate acetoacetate hydrolase (FAH). Together, these results indicated that the liver can be perceived as the major target tissue of OBS, which strongly affected metabolic function and ultimately led to an imbalance in the metabolism of lipids and TYR. In summary, maternal OBS exposure during pregnancy and lactation has toxic effects on the hepatic metabolism of dams and offspring, indicating that the toxic effects could obviously cross generations of mice, and we should pay more attention to understanding the health risk to both dams and offspring.
全氟化合物（PFCs）对哺乳动物的毒性最近受到了越来越多的关注。然而，母体在怀孕期间和哺乳期暴露于全氟辛烷磺酸钠（OBS）对母体（F0）和后代（F1）小鼠的肝功能的影响尚不清楚。结果表明，母体 OBS 处理不仅可以诱导脂质代谢功能障碍，还可以破坏 F0 和 F1 代肝脏中的氨基酸代谢。OBS 在肝脏中有明显的蓄积，并且在母体 OBS 暴露后，F0 和 F1 代的血清和肝脏甘油三酯（TG）水平增加。此外，母体 OBS 暴露改变了与脂质代谢（脂肪酸（FA）合成、TG 合成和转运）相关的基因的转录水平，并导致母体和 20 日龄小鼠后代（F1-20 d）的氨基酸水平发生变化。此外，OBS 对脂质代谢的调节主要依赖于过氧化物酶体增殖物激活受体γ（PPARγ）和分化簇 36（CD36）的激活。有趣的是，OBS 还可以通过增加 TYR 水平和下调延胡索酸乙酰乙酸水解酶（FAH）来扰乱酪氨酸（TYR）代谢。总之，母体在怀孕期间和哺乳期暴露于 OBS 对母体和后代的肝脏代谢具有毒性作用，表明毒性作用可以明显跨越小鼠的几代，我们应该更加注意了解对母体和后代的健康风险。
