GSE169528
piRNA pathway is essential for generating functional oocytes in golden hamster
Piwi-interacting RNAs (piRNAs) are small RNAs predominantly expressed in germ cells that function in gametogenesis in various species. Notably, PIWI-deficient female mice are fertile and mouse oocytes express a panel of small RNAs that do not appear widely representative of mammals. Thus, the function of piRNAs in mammalian oogenesis remains largely elusive. Here, we generated PIWIL1- and MOV10L1-deficient golden hamsters and found that all female and male mutants were sterile, with severe defects in embryogenesis and spermatogenesis, respectively. PIWIL1-deficient oocytes displayed aberrant transposon accumulation and broad transcriptomic dysregulation, and maternal PIWIL1-deficient embryos had impaired zygotic genome activation (ZGA). Moreover, our results support that PIWIL1-piRNAs exert a non-redundant function in silencing endogenous retroviruses (ERVs) in oocytes. Together, our findings demonstrate that piRNAs are indispensable for generating functional germ cells in golden hamsters and show the informative value of this model species for functional and mechanistic investigations of piRNAs in gametogenesis, especially those related to female infertility. Overall design: Small and long RNAs profiling of developing oocytes and early embryos in wild-type and PIWIL1-deficient golden hamster females, as well as profiling of smRNAs after oxidation or PIWIL1- and PIWIL3-IP in MII stage oocytes or testis of wild-types and PIWIL1-mutents.