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Unaltered hepatic wound healing response in male rats with ancestral liver injury

Author

Listed:
  • Johanna Beil

    (Novartis, Biomedical Research)

  • Juliane Perner

    (Novartis, Biomedical Research)

  • Lena Pfaller

    (Novartis, Biomedical Research)

  • Marie-Apolline Gérard

    (Novartis, Biomedical Research)

  • Alessandro Piaia

    (Novartis, Biomedical Research)

  • Arno Doelemeyer

    (Novartis, Biomedical Research)

  • Adi Wasserkrug Naor

    (Novartis, Biomedical Research)

  • Lori Martin

    (Novartis, Biomedical Research)

  • Aline Piequet

    (Novartis, Biomedical Research)

  • Valérie Dubost

    (Novartis, Biomedical Research)

  • Salah-Dine Chibout

    (Novartis, Biomedical Research)

  • Jonathan Moggs

    (Novartis, Biomedical Research)

  • Rémi Terranova

    (Novartis, Biomedical Research)

Abstract

The possibility that ancestral environmental exposure could result in adaptive inherited effects in mammals has been long debated. Numerous rodent models of transgenerational responses to various environmental factors have been published but due to technical, operational and resource burden, most still await independent confirmation. A previous study reported multigenerational epigenetic adaptation of the hepatic wound healing response upon exposure to the hepatotoxicant carbon tetrachloride (CCl4) in male rats. Here, we comprehensively investigate the transgenerational effects by repeating the original CCl4 multigenerational study with increased power, pedigree tracing, F2 dose-response and suitable randomization schemes. Detailed pathology evaluations do not support adaptive phenotypic suppression of the hepatic wound healing response or a greater fitness of F2 animals with ancestral liver injury exposure. However, transcriptomic analyses identified genes whose expression correlates with ancestral liver injury, although the biological relevance of this apparent transgenerational transmission at the molecular level remains to be determined. This work overall highlights the need for independent evaluation of transgenerational epigenetic inheritance paradigms in mammals.

Suggested Citation

  • Johanna Beil & Juliane Perner & Lena Pfaller & Marie-Apolline Gérard & Alessandro Piaia & Arno Doelemeyer & Adi Wasserkrug Naor & Lori Martin & Aline Piequet & Valérie Dubost & Salah-Dine Chibout & Jo, 2023. "Unaltered hepatic wound healing response in male rats with ancestral liver injury," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41998-w
    DOI: 10.1038/s41467-023-41998-w
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    References listed on IDEAS

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    1. Bernhard Horsthemke, 2018. "A critical view on transgenerational epigenetic inheritance in humans," Nature Communications, Nature, vol. 9(1), pages 1-4, December.
    2. M. L. Richter & I. K. Deligiannis & K. Yin & A. Danese & E. Lleshi & P. Coupland & C. A. Vallejos & K. P. Matchett & N. C. Henderson & M. Colome-Tatche & C. P. Martinez-Jimenez, 2021. "Single-nucleus RNA-seq2 reveals functional crosstalk between liver zonation and ploidy," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    3. Giacomo Cavalli & Edith Heard, 2019. "Advances in epigenetics link genetics to the environment and disease," Nature, Nature, vol. 571(7766), pages 489-499, July.
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