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Research Paper|Volume 11, Issue 10|pp 2968—2997

The small non-coding RNA profile of mouse oocytes is modified during aging

Bettina P. Mihalas1,2, Nicole J. Camlin3, Miguel J. Xavier1, Alexandra E. Peters1,2, Janet E. Holt1, Jessie M. Sutherland1,2, Eileen A. McLaughlin1,2,4,5, Andrew L. Eamens6, Brett Nixon1,2
  • 1Priority Research Centre for Reproductive Science, Schools of Environmental and Life Sciences and Biomedical Science and Pharmacy, the University of Newcastle, Callaghan, New South Wales 2308, Australia
  • 2Pregnancy and Reproduction Program, Hunter Medical Research Institute, New Lambton Heights, New South Wales 2305, Australia
  • 3Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21218, United States
  • 4School of Biological Sciences, University of Auckland, Auckland 1142, New Zealand
  • 5School of Science, the University of Canberra, Bruce, Australian Capital Territory 2617, Australia
  • 6School of Environmental and Life Sciences, the University of Newcastle, Callaghan, New South Wales 2308, Australia
Received: February 14, 2019Accepted: April 29, 2019Published: May 24, 2019
https://doi.org/10.18632/aging.101947

Copyright: Mihalas et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Oocytes are reliant on messenger RNA (mRNA) stores to support their survival and integrity during a protracted period of transcriptional 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-protein-coding RNAs (sRNAs) is similarly altered in aged mouse oocytes. The application of high throughput sequencing revealed substantial changes to the global sRNA profile of germinal vesicle stage oocytes from young (4-6 weeks) and aged mice (14-16 months). Among these, 160 endogenous small-interfering RNAs (endo-siRNAs) and 10 microRNAs (miRNAs) were determined to differentially accumulate within young and aged oocytes. Further, we revealed decreased expression of two members of the kinesin protein family, Kifc1 and Kifc5b, in aged oocytes; family members selectively targeted for expression regulation by endo-siRNAs of elevated abundance. 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 altered sRNA abundance, specifically endo-siRNA abundance, could influence the quality of the aged oocyte.