Formation of spermatogonia and fertile oocytes in golden hamsters requires piRNAs

Zuzana Loubalova,Josef Pasulka,Michiko Hirose,Helena Fulka,Atsuo Ogura,Filip Horvat,Petr Svoboda,Radek Malik

doi:10.1038/s41556-021-00746-2

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.

Highlights

PIWI-interacting RNAs support the germline by suppressing retrotransposons
Loss of MOV10L1 or PIWI proteins in mice revealed specific essential roles of PIWI-interacting RNAs (piRNAs) in spermatogenesis but not in oogenesis[3,4,13,14,15,16]. It is unclear whether the dispensability of piRNAs in females is common among mammals. piRNAs target retrotransposons during mouse oogenesis[17,18], but the maternal piRNA pathway is partially redundant with RNA interference (RNAi)[19]
Mice lack PIWIL3, which binds to 19–20-nucleotide piRNAs in human and golden hamster oocytes and exists in many mammals, suggesting that there is a major difference between oocyte piRNA biology in mice versus other mammals[10,11,21]

Summary

Introduction

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. Loss of MOV10L1 or PIWI proteins in mice revealed specific essential roles of piRNAs in spermatogenesis but not in oogenesis[3,4,13,14,15,16] It is unclear whether the dispensability of piRNAs in females is common among mammals. Mice lack PIWIL3, which binds to 19–20-nucleotide piRNAs in human and golden hamster oocytes and exists in many mammals, suggesting that there is a major difference between oocyte piRNA biology in mice versus other mammals[10,11,21] It is unclear whether differences in the piRNA pathway set-up are associated with biologically important roles. In contrast to mice and similar to humans, golden hamster retained four PIWI paralogues expressed in the germline and its oocytes probably lack highly active RNAi27

Methods

Results

Conclusion