Hypoxia Induces Transgenerational Epigenetic Inheritance of Small RNAs

Animals sense and adapt to decreased oxygen availability, but whether and how hypoxia exposure in ancestors can elicit phenotypic consequences in normoxia reared descendants is still unknown. Here, 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 both repressive histone modifying enzymes and the argonaute HRDE-1. Feeding naïve C. elegans with 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 parental hypoxia and soaking naïve normoxia reared C. elegans with F44E5.4/5 dsRNA is sufficient to induce an intergenerational fertility defect. Finally, we demonstrate that labelled F44E5.4/5 dsRNA is itself transmitted from parents to children. Our results suggest that small RNAs respond to the environment, are transmitted from ancestors to their descendants, and are sufficient to transmit non-genetic information from parents to their naïve children.