Perfluorooctanesulfonic acid exposure altered hypothalamic metabolism and disturbed male fecundity

Zijie Li, Ziyi Lin, Shuqin Ji, Keng Po Lai, Hin Ting Wan, Chris Kong Chu Wong*, Lei Li*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

12 Citations (Scopus)


Previous studies have examined the effects of perfluorooctanesulfonic acid (PFOS) on disruption of the blood-testis barrier and spermatogenesis. Sertoli and Leydig cells were perturbed, resulting in a decrease in testosterone levels and sperm counts. However, the effects of PFOS on male fecundity are not limited to the testes. In this study, we demonstrated that oral PFOS exposure (1 μg/g BW and 5 μg/g BW) decreased the function of the Luteinizing hormone (LH)/Luteinizing hormone receptor (LHr) and decreased epididymal sperm motility. Consistently, testicular transcriptome analysis revealed that PFOS altered the expression of a cluster of genes associated with sperm motility and steroidogenesis. In mice exposed to PFOS, c-Fos immunostaining showed activation of the lateral septal nucleus (LS), paraventricular thalamus (PVT), locus coeruleus (LC), which are known to be related to anxiety-like behaviors. Metabolomic analyses of the hypothalamus revealed that exposure to PFOS perturbed the translation of proteins, as well as the biosynthesis of neurotransmitters and neuromodulators. Altogether, the activation of brain nuclei, shift of hypothalamic metabolome, and reduction of LH/LHr circuit resulted from PFOS exposure suggested the toxicant's systematic effects on male reproduction.

Original languageEnglish
Article number156881
JournalScience of the Total Environment
Early online date23 Jun 2022
Publication statusPublished - 20 Oct 2022

Scopus Subject Areas

  • Environmental Engineering
  • Environmental Chemistry
  • Waste Management and Disposal
  • Pollution

User-Defined Keywords

  • Hypothalamus
  • Locus coeruleus
  • Metabolome
  • PFOS
  • Transcriptome


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