Hypoxia induces transgenerational epigenetic inheritance of small RNAs

Cell Rep. 2022 Dec 13;41(11):111800. doi: 10.1016/j.celrep.2022.111800.


Animals sense and adapt to decreased oxygen availability, but whether and how hypoxia exposure in ancestors can elicit phenotypic consequences in normoxia-reared descendants are unclear. We show that hypoxia educes an intergenerational reduction in lipids and a transgenerational reduction in fertility in the nematode Caenorhabditis elegans. The transmission of these epigenetic phenotypes is dependent on repressive histone-modifying enzymes and the argonaute HRDE-1. Feeding naive C. elegans small RNAs extracted from hypoxia-treated worms is sufficient to induce a fertility defect. Furthermore, the endogenous small interfering RNA F44E5.4/5 is upregulated intergenerationally in response to hypoxia, and soaking naive normoxia-reared C. elegans with F44E5.4/5 double-stranded RNA (dsRNA) is sufficient to induce an intergenerational fertility defect. Finally, we demonstrate that labeled F44E5.4/5 dsRNA is itself transmitted from parents to children. Our results suggest that small RNAs respond to the environment and are sufficient to transmit non-genetic information from parents to their naive children.

Keywords: C. elegans; CP: Molecular biology; F44E5.4/5; HRDE-1; germ granule; hypoxia; small RNA; transgenerational epigenetic inheritance.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Caenorhabditis elegans Proteins* / genetics
  • Caenorhabditis elegans Proteins* / metabolism
  • Caenorhabditis elegans* / genetics
  • Caenorhabditis elegans* / metabolism
  • Epigenesis, Genetic
  • Hypoxia / genetics
  • Inheritance Patterns
  • RNA Interference
  • RNA, Double-Stranded / genetics
  • RNA, Small Interfering / genetics


  • Caenorhabditis elegans Proteins
  • RNA, Small Interfering
  • RNA, Double-Stranded