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RNA

Golden opportunity for piRNA in female fertility

Nature Cell Biology volume 23, pages 936–938 (2021)Cite this article

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Mice deficient in the piRNA pathway display sterility only in males. Taking advantage of a more representative piRNA pathway in golden hamsters, three studies now demonstrate that the piRNA pathway is essential for fertility in hamsters of both sexes and thus strongly link this small RNA pathway to fertility regulation in both men and women.

The piRNA pathway is an adaptive mechanism that safeguards genome integrity from transposable elements (TEs) in the germline by silencing active transposons through targeted degradation of TE transcripts and epigenetic silencing of TE genomic loci. piRNAs are small non-coding RNAs that are associated with members of the PIWI family of proteins. More than 20 evolutionarily conserved proteins are involved in the piRNA pathway. In mice, there are three PIWI paralogues: PIWIL1, PIWIL2 and PIWIL4. MOV10L1, a germ cell–specific RNA helicase, interacts with all PIWI proteins and binds to piRNA precursors to initiate piRNA biogenesis1,2,3. In fruit flies and zebrafish, disruption of piRNA pathway components affects the fertility of both sexes4,5. However, mutant mice lacking any of the Piwi genes or genes encoding any of the other components of the piRNA pathway exhibit fertility defects in males but not in females6,7,8, which has led to the general perception that the piRNA pathway is not required for female fertility in mammals. That notion is reinforced by the existence of robust RNA interference endowed by the oocyte-specific Dicer isoform in mice, which lessens the dependence of TE silencing on piRNAs in mouse oocytes9. The identification of PIWIL3, a fourth PIWI protein expressed specifically in the oocytes of many mammals, including humans, but not in mice, raises the possibility that mice might be the exception rather than the rule in the piRNA pathway. Notably, three studies of golden hamsters by Hasuwa et al.10, Loubalova et al.11 and Zhang et al.12 in this issue of Nature Cell Biology demonstrate that PIWI proteins, MOV10L1 and piRNAs are essential for the production of both functional oocytes and male gametes in mammals.

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Fig. 1: Sexually dimorphic requirement for the piRNA pathway in mice but not golden hamsters.

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  1. Department of Biomedical Sciences, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA, USA

    Yongjuan Guan & P. Jeremy Wang

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  1. Yongjuan Guan
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Correspondence to P. Jeremy Wang.

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Guan, Y., Wang, P.J. Golden opportunity for piRNA in female fertility. Nat Cell Biol 23, 936–938 (2021). https://doi.org/10.1038/s41556-021-00749-z

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