Meiotic maturation failure induced by DICER1 deficiency is derived from primary oocyte ooplasm

Abstract

RNA interference (RNAi) has diverse functions across cellular processes, including a role in the development of the mammalian oocyte. Mouse primary oocytes deficient in the key RNAi enzyme DICER1 exhibit pronounced defects in chromosome congression and spindle formation during meiotic maturation. The cause of this meiotic maturation failure is unknown. In this study, observations of chromosomes and spindle microtubules during prometaphase in DICER1-deficient oocytes indicate that chromosome congression and spindle formation are overtly normal. Spindle breakdown and chromosome displacement occur after the metaphase plate has formed, during the metaphase to anaphase transition. We hypothesised that this defect could be attributed to either RNAi-mediated regulation of nuclear factors, such as the regulation of centromere chromatin assembly, or the regulation of mRNA expression within the cytoplasm. By transplanting germinal vesicles between DICER1-deficient and wild-type primary oocytes, we show that, unexpectedly, the meiotic failure is not caused by a deficiency derived from the germinal vesicle component. Instead, we reveal that the ooplasm of primary oocytes contains DICER1-dependent factors that are crucial for chromosome segregation and meiotic maturation.