piRNA pathway is essential for generating functional oocytes in golden hamster

Piwi-interacting RNAs (piRNAs) are small RNAs predominantly expressed in germ cells that are critical for gametogenesis in various species. However, PIWI-deficient female mice are fertile and mouse oocytes express a panel of small RNAs that do not appear widely representative of mammals, and piRNA function in the oogenesis of other mammals has therefore remained elusive. Recent studies revealed the small RNA and PIWI transcriptional profiles in golden hamster oocytes more closely resemble that of humans than mice. Herein, we generated PIWIL1-, PLD6- and MOV10L1-deficient golden hamsters and found that all female mutants were sterile, with embryos arrested at the two-cell stage. In PIWIL1 mutant oocytes, we observed transposon accumulation and broad transcriptomic dysregulation, while zygotic gene activation was impaired in early embryos. Intriguingly, PIWIL1-piRNAs exhibited a unique, preferential silencing of endogenous retroviruses (ERVs), whereas silencing LINE1s depended on both PIWIL1- and PIWIL3-piRNAs. Moreover, we showed that piRNAs participate in the degradation of maternal mRNAs in MII oocytes and embryos via partially complementary targets. Together, our findings demonstrate that piRNAs are indispensable for generating functional oocytes in golden hamster, and show the informative value of this model for functional and mechanistic investigations of piRNAs, especially those related to female infertility.