Abstract
Defective Piwi/piRNA genome silencing leads to heterochromatin dysfunction and immediate sterility in many species. Sterile Piwi mutants experience transposon expression and transposon-induced genomic instability, although the cause of Piwi mutant sterility remains uncertain. C. elegans germ cells deficient for Piwi pathway genome silencing factors transmit a form of heritable stress that induces sterility after growth for several generations, allowing comparisons of animals that are close to sterility but fertile with sterile siblings. Sterile Piwi pathway mutants displayed inconsistent increases in DNA damage signaling but consistently altered perinuclear liquid droplets termed germ granules. Germ granule dysfunction did not elicit significant levels of transposon expression but was sufficient to induce a range of idiosyncratic phenotypes associated with sterile Piwi pathway genome silencing mutants, including germline atrophy, reproductive arrest and univalents in oocytes. Expression of genes that perturb germ granule structure was not compromised in sterile Piwi pathway mutants, suggesting that a post-transcriptional mechanism regulates the stability of Piwi mutant germ granules. We propose that sterility in response to transgenerational deficiency for Piwi and in response to acute dysfunction of germ granules occur as a consequence of a common reproductive arrest mechanism. The germ granule abnormalities of sterile Piwi pathway mutants therefore suggest germ granule dysfunction as a cause of Piwi mutant sterility.