Effects of In Utero PFOS Exposure on Epigenetics and Metabolism in Mouse Fetal Livers

Tsz Chun Ho, Hin Ting Wan, Wang Ka Lee, Thomas Ka Yam Lam, Xiao Lin, Ting Fung Chan, Keng Po Lai, Chris Kong Chu Wong*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

6 Citations (Scopus)

Abstract

Prenatal exposure to perfluorooctanesulfonate (PFOS) increases fetus’ metabolic risk; however, the investigation of the underlying mechanism is limited. In this study, pregnant mice in the gestational days (GD, 4.5–17.5) were exposed to PFOS (0.3 and 3 μg/g of body weight). At GD 17.5, PFOS perturbed maternal lipid metabolism and upregulated metabolism-regulating hepatokines (Angptl4, Angptl8, and Selenop). Mass-spectrometry imaging and whole-genome bisulfite sequencing revealed, respectively, selective PFOS localization and deregulation of gene methylation in fetal livers, involved in inflammation, glucose, and fatty acid metabolism. PCR and Western blot analysis of lipid-laden fetal livers showed activation of AMPK signaling, accompanied by significant increases in the expression of glucose transporters (Glut2/4), hexose-phosphate sensors (Retsat and ChREBP), and the key glycolytic enzyme, pyruvate kinase (Pk) for glucose catabolism. Additionally, PFOS modulated the expression levels of PPARα and PPARγ downstream target genes, which simultaneously stimulated fatty acid oxidation (Cyp4a14, Acot, and Acox) and lipogenesis (Srebp1c, Acaca, and Fasn). Using human normal hepatocyte (MIHA) cells, the underlying mechanism of PFOS-elicited nuclear translocation of ChREBP, associated with a fatty acid synthesizing pathway, was revealed. Our finding implies that in utero PFOS exposure altered the epigenetic landscape associated with dysregulation of fetal liver metabolism, predisposing postnatal susceptibility to metabolic challenges.
Original languageEnglish
Pages (from-to)14892-14903
Number of pages12
JournalEnvironmental Science and Technology
Volume57
Issue number40
Early online date27 Sept 2023
DOIs
Publication statusPublished - 10 Oct 2023

Scopus Subject Areas

  • Chemistry(all)
  • Environmental Chemistry

User-Defined Keywords

  • AMPK
  • ChREBP
  • MIHA
  • MS-imaging
  • PPAR
  • hepatokine
  • whole-genome bisulfite sequencing

Fingerprint

Dive into the research topics of 'Effects of In Utero PFOS Exposure on Epigenetics and Metabolism in Mouse Fetal Livers'. Together they form a unique fingerprint.

Cite this