Formation of spermatogonia and fertile oocytes in golden hamsters requires piRNAs

Abstract

PIWI-interacting RNAs (piRNAs) support the germline by suppressing retrotransposons. Studies of the pathway in mice have strongly shaped the view that mammalian piRNAs are essential for male but not for female fertility. Here, we report that the role of the piRNA pathway substantially differs in golden hamsters (Mesocricetus auratus), the piRNA pathway setup of which more closely resembles that of other mammals, including humans. The loss of the Mov10l1 RNA helicase—an essential piRNA biogenesis factor—leads to striking phenotypes in both sexes. In contrast to mice, female Mov10l1–/– hamsters are sterile because their oocytes do not sustain zygotic development. Furthermore, Mov10l1–/– male hamsters have impaired establishment of spermatogonia accompanied by transcriptome dysregulation and an expression surge of a young retrotransposon subfamily. Our results show that the mammalian piRNA pathway has essential roles in both sexes and its adaptive nature allows it to manage emerging genomic threats and acquire new critical roles in the germline.

Taming transposable elements in vertebrates: from epigenetic silencing to domestication

“…The sexual asymmetry of the piRNA pathway in murine male and female germlines may be an exception in mammals. In fact, other mammals encode a fourth Piwi gene not encoded in Muridae: Piwil3 (Table 1) [58][59][60][61][62]182]. The non-Muridae rodent Mesocricetus auratus, the golden hamster, has recently emerged as a novel model, likely more representative of mammalian piRNA pathways [58][59][60]62].…”

“…In fact, other mammals encode a fourth Piwi gene not encoded in Muridae: Piwil3 (Table 1) [58][59][60][61][62]182]. The non-Muridae rodent Mesocricetus auratus, the golden hamster, has recently emerged as a novel model, likely more representative of mammalian piRNA pathways [58][59][60]62]. Piwil1 mutant golden hamsters are sterile irrespective of the sex and PIWIL1/piRNA complexes are engaged in TE silencing in oocytes [58,62].…”

High-resolution Ribosome Profiling Reveals Translational Selectivity for Transcripts in Bovine Preimplantation Embryo Development

“…In this study, the fractions of free RNAs (F1 and F2) were excluded because of the discontinuity with the other fractions in the global expression pattern (Figure 1B) and also because no ribosome bound RNA by qPCR analysis as described above. We anticipated the largely free RNA (not attached to any ribosome or protein) in F1-F2s might include microRNAs or non-coding RNAs, which play a significant function in early development based on recently studies (68–71). The inadequate annotation of such RNAs in bovine genome also limited the comprehensive characterizations in this study.…”

Roles of Noncoding RNA in Reproduction

“…Interestingly, PIWIL1-deficient females had normal ovaries and were able to produce mature oocytes, but the fertilized eggs produced by mating with wild-type males did not develop properly and remained stuck in the two-cell stage. It was found that the deletion of PIWIL1 gene resulted in abnormal accumulation of transposons in oocytes, decreased degradation of maternal mRNA and failure of zygotic gene activation during early embryonic development ( Hasuwa et al, 2021 ; Loubalova et al, 2021 ). These results suggest that piRNA pathway may also play an important role in human and other mammalian female reproduction, providing an important theoretical basis and animal model for the diagnosis and treatment of piRNA pathway abnormalities and female reproductive diseases.…”