Perfluorooctane sulfonate interferes with non-genomic estrogen receptor signaling pathway, inhibits ERK1/2 activation and induces apoptosis in mouse spermatocyte-derived cells.

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  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: Ireland NLM ID: 0361055 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-3185 (Electronic) Linking ISSN: 0300483X NLM ISO Abbreviation: Toxicology Subsets: MEDLINE
    • Publication Information:
      Publication: Limerick : Elsevier
      Original Publication: Amsterdam. Elsevier/North-Holland.
    • Subject Terms:
      Alkanesulfonic Acids/*toxicity ; Apoptosis/*drug effects ; Fluorocarbons/*toxicity ; MAP Kinase Signaling System/*drug effects ; Receptors, Estrogen/*antagonists & inhibitors ; Spermatocytes/*drug effects; Animals ; Apoptosis/physiology ; Cell Line ; Cell Survival/drug effects ; Cell Survival/physiology ; Chlorocebus aethiops ; Dose-Response Relationship, Drug ; MAP Kinase Signaling System/physiology ; Male ; Mice ; Receptors, Estrogen/metabolism ; Signal Transduction/drug effects ; Signal Transduction/physiology ; Spermatocytes/metabolism
    • Abstract:
      Perfluorooctane sulfonate (PFOS) is a widespread persistent organic pollutant. Both epidemiological survey and our previous in vivo study have revealed the associations between PFOS exposure and spermatogenesis disorder, while the underlying mechanisms are far from clear. In the present study, GC-2 cells, a mouse spermatocyte-derived cell line, was used to investigate the toxic effects of PFOS and its hypothetical mechanism of action. GC-2 cells were treated with PFOS (0, 50, 100 and 150 μM) for 24 h or 48 h. Results demonstrated that PFOS dose-dependently inhibited cell viability, induced G0/G1 cell cycle arrest and triggered apoptosis, which might be partly explained by the decrease in cyclin D1, PCNA and Bcl-2 protein expression; increase in Bax protein expression; and activation of caspase-9, -3. In addition, PFOS did not directly transactivate or repress estrogen receptors (ERs) in gene reporter assays, whereas the protein levels of both ERα and ERβ were significantly altered and the downstream ERK1/2 phosphorylation was inhibited by PFOS. Furthermore, pretreatment with specific ERα agonist PPT (1 μM) significantly attenuated the above PFOS-induced effects while specific ERβ agonist DPN (1 μM) accelerated them. These results suggest that PFOS may induce growth inhibition and apoptosis via non-genomic estrogen receptor/ERK1/2 signaling pathway in GC-2 cells, which provides a novel insight regarding the potential role of ERs in mediating PFOS-triggered spermatocyte toxicity.
      (Copyright © 2021 Elsevier B.V. All rights reserved.)
    • Contributed Indexing:
      Keywords: ERK1/2 signaling; Estrogen receptor; Mouse spermatocyte-derived GC-2 cells; PFOS
    • Accession Number:
      0 (Alkanesulfonic Acids)
      0 (Fluorocarbons)
      0 (Receptors, Estrogen)
      9H2MAI21CL (perfluorooctane sulfonic acid)
    • Publication Date:
      Date Created: 20210725 Date Completed: 20211005 Latest Revision: 20211005
    • Publication Date:
      20240829
    • Accession Number:
      10.1016/j.tox.2021.152871
    • Accession Number:
      34303733