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Transcriptome and Metabolome Analyses Reveal Perfluorooctanoic Acid-Induced Kidney Injury by Interfering with PPAR Signaling Pathway

后代 转录组 超氧化物歧化酶 生物 氧化应激 内分泌学 内科学 代谢组 丙二醛 过氧化物酶体增殖物激活受体 生物化学 受体 代谢物 基因表达 怀孕 基因 医学 遗传学
作者
Yan Zhang,Li Yang,Nana Gao,Yinglan Gong,Wanyu Shi,Xiaodan Wang
出处
期刊:International Journal of Molecular Sciences [MDPI AG]
卷期号:24 (14): 11503-11503 被引量:8
标识
DOI:10.3390/ijms241411503
摘要

Perfluorooctanoic acid (PFOA) is widely used in aviation science and technology, transportation, electronics, kitchenware, and other household products. It is stable in the environment and has potential nephrotoxicity. To investigate the effect of PFOA exposure during pregnancy on the kidneys of offspring mice, a total of 20 mice at day 0 of gestation were randomly divided into two groups (10 mice in each group), and each group was administered 0.2 mL of PFOA at a dose of 3.5 mg/kg or deionized water by gavage during gestation. The kidney weight, kidney index, histopathological observation, serum biochemistry, transcriptomics, and metabolomics of the kidneys of the 35-day offspring mice were analyzed. In addition, malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) levels in the kidney were measured. Transcriptome analysis results showed that 387 genes were up-regulated and 283 genes were down-regulated compared with the control group. These differentially expressed genes (DEGs) were mainly concentrated in the peroxisome-proliferator-activated receptor (PPAR) signaling pathway and circadian rhythm. Compared with the control group, 64 and 73 metabolites were up- and down-regulated, respectively, in the PFOA group. The altered metabolites were mainly enriched in the biosynthesis of unsaturated fatty acids. PFOA can affect the expression levels of circadian rhythm-related genes in the kidneys of offspring mice, and this change is influenced by the PPAR signaling pathway. PFOA causes oxidative stress in the kidneys, which is responsible for significant changes in metabolites associated with the biosynthesis of unsaturated fatty acids.
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