Production of functional oocytes requires maternally expressed PIWI genes and piRNAs in golden hamsters

• Published in: Nature cell biology Vol. 23; no. 9; pp. 1002 - 1012
• Main Authors: Hasuwa, Hidetoshi, Iwasaki, Yuka W., Au Yeung, Wan Kin, Ishino, Kyoko, Masuda, Harumi, Sasaki, Hiroyuki, Siomi, Haruhiko
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.09.2021; Nature Publishing Group
• Subjects: 38; 45; 631/136/2434/1706; 631/136/2434/1822; 631/337/384/2054; 64; Analysis; Biomedical and Life Sciences; Cancer Research; Cell Biology; Deoxyribonucleic acid; Developmental Biology; DNA; DNA methylation; Fertility; Gametocytes; Gene expression; Genes; Genetic aspects; Genomes; Hamsters; Life Sciences; Mammals; Methylation; Oocytes; Perturbation; RNA; Sex differences; Stem Cells; Sterility; Japan
• ISSN: 1465-7392; 1476-4679
• DOI: 10.1038/s41556-021-00745-3

Many animals have a conserved adaptive genome defence system known as the Piwi-interacting RNA (piRNA) pathway, which is essential for germ cell development and function. Disruption of individual mouse Piwi genes results in male but not female sterility, leading to the assumption that PIWI genes play little or no role in mammalian oocytes. Here, we report the generation of PIWI-defective golden hamsters, which have defects in the production of functional oocytes. The mechanisms involved vary among the hamster PIWI genes, whereby the lack of PIWIL1 has a major impact on gene expression, including hamster-specific young transposon de-silencing, whereas PIWIL3 deficiency has little impact on gene expression in oocytes, although DNA methylation was reduced to some extent in PIWIL3 -deficient oocytes. Our findings serve as the foundation for developing useful models to study the piRNA pathway in mammalian oocytes, including humans. A set of three papers reports that the piRNA pathway is essential for mammalian female fertility based on genetic perturbation experiments performed in golden hamsters.