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

Bettina P. Mihalas, Nicole J. Camlin, Miguel J. Xavier, Alexandra E. Peters, Janet E. Holt, Jessie M. Sutherland, Eileen A. McLaughlin, Andrew L. Eamens, Brett Nixon

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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.

Original languageEnglish
Pages (from-to)2968-2997
Number of pages30
JournalAging
Volume11
Issue number10
DOIs
Publication statusPublished - 31 May 2019

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Small Untranslated RNA
Oocytes
Small Interfering RNA
Kinesin
Messenger RNA
Aneuploidy
Ovulation
MicroRNAs
Pharmacology

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Mihalas, B. P., Camlin, N. J., Xavier, M. J., Peters, A. E., Holt, J. E., Sutherland, J. M., ... Nixon, B. (2019). The small non-coding RNA profile of mouse oocytes is modified during aging. Aging, 11(10), 2968-2997. https://doi.org/10.18632/aging.101947
Mihalas, Bettina P. ; Camlin, Nicole J. ; Xavier, Miguel J. ; Peters, Alexandra E. ; Holt, Janet E. ; Sutherland, Jessie M. ; McLaughlin, Eileen A. ; Eamens, Andrew L. ; Nixon, Brett. / The small non-coding RNA profile of mouse oocytes is modified during aging. In: Aging. 2019 ; Vol. 11, No. 10. pp. 2968-2997.
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Mihalas, BP, Camlin, NJ, Xavier, MJ, Peters, AE, Holt, JE, Sutherland, JM, McLaughlin, EA, Eamens, AL & Nixon, B 2019, 'The small non-coding RNA profile of mouse oocytes is modified during aging', Aging, vol. 11, no. 10, pp. 2968-2997. https://doi.org/10.18632/aging.101947

The small non-coding RNA profile of mouse oocytes is modified during aging. / Mihalas, Bettina P.; Camlin, Nicole J.; Xavier, Miguel J.; Peters, Alexandra E.; Holt, Janet E.; Sutherland, Jessie M.; McLaughlin, Eileen A.; Eamens, Andrew L.; Nixon, Brett.

In: Aging, Vol. 11, No. 10, 31.05.2019, p. 2968-2997.

Research output: Contribution to journalArticle

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AU - Mihalas, Bettina P.

AU - Camlin, Nicole J.

AU - Xavier, Miguel J.

AU - Peters, Alexandra E.

AU - Holt, Janet E.

AU - Sutherland, Jessie M.

AU - McLaughlin, Eileen A.

AU - Eamens, Andrew L.

AU - Nixon, Brett

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AB - 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.

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Mihalas BP, Camlin NJ, Xavier MJ, Peters AE, Holt JE, Sutherland JM et al. The small non-coding RNA profile of mouse oocytes is modified during aging. Aging. 2019 May 31;11(10):2968-2997. https://doi.org/10.18632/aging.101947