Distinctively Different Effects of Perfluorobutanoic Acid and Perfluorononanoic Acid on Zebrafish Sex Differentiation and Androgen Receptor Activity

  • Environ Health (Wash). 2025 Jan 27;3(5):482-492. doi: 10.1021/envhealth.4c00240.
Tingyu Lu  1  2 ,  Wei Zheng  2 ,  Yuyang Lei  2 ,  Fanglin Hu  2 ,  Minjie Li  3 ,  Liang-Hong Guo  1  3
Affiliations
  • 1. School of Environment, Hangzhou Institute for Advanced Study, University of the Chinese Academy of Sciences, Hangzhou, Zhejiang 310024, China.
  • 2. College of Life Science, China Jiliang University, Hangzhou, Zhejiang 310018, China.
  • 3. College of Energy Environment and Safety Engineering, China Jiliang University, Hangzhou, Zhejiang 310018, China.
PMID: 40400555 DOI: 10.1021/envhealth.4c00240
Abstract

With the prohibition of perfluorooctanoic acid (PFOA), the emergence of alternative perfluoroalkyl substances such as perfluorobutanonic acid (PFBA) and perfluorononanoic acid (PFNA) in various environmental matrices has led to concerns about their adverse effects on humans and biota. This study aims to investigate the reproductive and developmental toxicity of PFBA and PFNA by combined in vivo, in vitro, and in silico approaches. Examination of juvenile zebrafish exposed to PFBA at environmental concentrations by histopathology, sex hormone, and gene expression revealed accelerated development of zebrafish toward males, while exposure to PFNA during sex differentiation resulted in feminization. In accordance with the in vivo results, PFBA activated the Androgen Receptor (AR) signaling pathway, but PFNA inhibited it in both prostate Cancer cell proliferation and luciferase reporter gene assays. Similarly, the differential binding mode of the two chemicals to AR was shown in the molecular docking analysis, with PFBA exhibiting higher potency for the agonist conformation and PFNA favoring the antagonistic conformation. Together, these results suggest that, while PFNA exhibited similar effects on sex differentiation and AR activity as PFOA, PFBA showed distinctive effects and deserves particular attention and further investigation.

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