Soma-to-germline miRNA inheritance through yolk promotes stress resilience in progeny.

At the onset of reproduction, oviparous animals synthesize large amounts of yolk in somatic tissues to provide lipids and other nutrients to their progeny. However, whether the yolk transports other molecules, such as RNAs with gene-regulatory functions, remains largely unexplored. Here, we biochemically purified the yolk granules in the nematode Caenorhabditis elegans and show they contain microRNAs (miRNAs). We provide evidence that the yolk transports miRNAs from the intestine of the mother to the embryos by the lipoprotein yolk receptor RME-2. These yolk-enriched miRNAs inherited by the embryos regulate the transcriptomes of developing larvae. Moreover, environmental stresses and maternal age modulate the transfer of yolk-enriched miRNAs, contributing to stress-resilience benefits to progeny. This discovery establishes an alternative paradigm in intergenerational gene regulation, where the gut-germline axis orchestrates the transmission of environmental cues through yolk-enriched miRNAs. Our work, thus, reveals a mechanism underlying the soma-to-germline transfer of epigenetic information in animals.