Increased expression of Kifc1 and Kifc5b targeting endogenous-siRNA contribute to the age-related decline in oocyte quality

The oocyte is reliant on stores of endogenous mRNA transcripts in order to support their survival and integrity during a protracted period of dormancy as they await ovulation. Oocytes are however, known to experience an age-associated alteration in mRNA transcript abundance, a phenomenon that contributes to reduced developmental potential. Here we have investigated whether the expression profile of small non-coding RNAs (sncRNAs) is similarly altered in aged mouse oocytes. The application of high throughput sequencing revealed substantial changes in the global sncRNA profile of germinal vesicle stage oocytes from young (4-6 weeks) and aged mice (14-16 months). Among these changes, we identified 160 endo-siRNA and ten microRNAs that differentially accumulated within young and aged oocytes. Several endo-siRNAs that were upregulated in aged oocytes selectively targeted Kifc1 and Kifc5b; members of the kinesin protein family that were confirmed as being reciprocally reduced in the aged oocytes. The implications of reduced Kifc1 and Kifc5b expression were explored using complementary siRNA-mediated knockdown and pharmacological inhibition strategies, both of which led to increased rates of aneuploidy in otherwise healthy young oocytes. Collectively, our data raise the prospect that dysregulation of sncRNA expression, particularly endo-siRNA, may contribute to the age-dependent deterioration of oocyte quality. Overall design: RNA-Seq was performed on a single biological replicate comprising of 582 young and 521 aged pooled oocytes, which were isolated from 18 and 49 animals, respectively