Paternal nicotine exposure promotes hepatic fibrosis in offspring

Dong Zhang, Jingbo Dai, Meixing Zhang, Yilin Xie, Yong Cao, Guang He, Wangjie Xu, Lianyun Wang, Zhiguang Qiao, Zhongdong Qiao*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Paternal nicotine exposure can alter phenotypes in future generations. The aim of this study is to explore whether paternal nicotine exposure affects the hepatic repair to chronic injury which leads to hepatic fibrosis in offspring. Our results demonstrate that nicotine down regulates mmu-miR-15b expression via the hyper-methylation on its CpG island shore region in the spermatozoa. This epigenetic modification imprinted in the liver of the offspring. The decreased mmu-miR-15b promotes the expression of Wnt4 and activates the Wnt pathway in the offspring mice liver. The activation of the Wnt pathway improves the activation and proliferation of hepatic stellate cells (HSCs) leading to liver fibrosis. Moreover, the Wnt pathway promotes the activation of the TGF-β pathway and the two pathways cooperate to promote the transcription of extracellular matrix (ECM) genes. In conclusion, this study found that nicotine promotes hepatic fibrosis in the offspring via the activation of Wnt pathway by imprinting the hyper-methylation of mmu-miR-15b.

Original languageEnglish (US)
Pages (from-to)44-55
Number of pages12
JournalToxicology Letters
StatePublished - Jun 1 2021


  • Hepatic fibrosis
  • Intergenerational transmission
  • Methylation
  • Nicotine
  • Wnt pathway

ASJC Scopus subject areas

  • Toxicology


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