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

Abstract

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.