PFOS-elicited metabolic perturbation in liver and fatty acid metabolites in testis of adult mice

Wang Ka Lee, Thomas Ka Yam Lam, Hiu Ching Tang, Tsz Chun Ho, Hin Ting Wan*, Chris Kong Chu Wong*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review


Introduction: Multiple factors can contribute to sub-fecundity, including genetics, lifestyle, and environmental contaminants. PFASs are characterized as “forever chemicals” due to their ubiquitous contamination and their persistence in the environment, wildlife, and humans. Numerous studies have demonstrated that PFAS exposure adversely affects multiple bodily functions, including liver metabolism and gonadal function. It is unclear, however, how the disruption of hepatic fatty acid metabolism affects testicular function. Methods: In this study, male mice were administered 0.3 and 3 μg/g body weight of PFOS for 21 days. Results: Our data showed that PFOS exposure caused hepatic steatosis, as evidenced by significant increases in triglyceride levels, expression of ATP-citrate lyase, and fatty acid synthase, as well as fasting insulin levels. PFOS perturbed the expression levels of hepatokines, of which fibroblast growth factor-21 (Fgf-21), leukocyte cell-derived chemotaxin-2 (Lect-2), and retinol-binding protein-4 (Rbp-4) were significantly reduced, whereas angiopoietin-like 4 (Angptl4) was noticeably increased. While Rbp-4 and Fgf-21 are known to contribute to spermatogenesis and testosterone synthesis. In PFOS-exposed groups, testicular ATP, and testosterone decreased significantly with a significant increase in the expression of peroxisome proliferator-activated receptor-coactivator 1α. Mass spectrophotometry imaging revealed the localization of PFOS in testes, along with significant increases in fatty acid metabolites. These included arachidonic acid, dihomo-α-linolenic acid, dihomo-γ-linolenic acid, oxidized ceramide, diacylglycerol, phosphatidylcholine, and phosphatidylethanolamine, which are associated with inflammation and post-testicular causes of infertility. Discussion: This study revealed potential links between PFOS-elicited changes in hepatic metabolism and their impacts on testicular biology. This study provides insights into alternative targets elicited by PFOS that can be used to develop diagnostic and therapeutic strategies for improving testicular dysfunction.

Original languageEnglish
Article number1302965
Number of pages10
JournalFrontiers in Endocrinology
Publication statusPublished - 22 Nov 2023

Scopus Subject Areas

  • Endocrinology, Diabetes and Metabolism

User-Defined Keywords

  • fecundity
  • hepatokines
  • lipogenesis
  • mass spectrophotometry imaging
  • testosterone


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