Related Experiment Video

Updated: Aug 12, 2025

Defining the Program of Maternal mRNA Translation during In vitro Maturation using a Single Oocyte Reporter Assay
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Defining the Program of Maternal mRNA Translation during In vitro Maturation using a Single Oocyte Reporter Assay

Published on: June 16, 2021

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CPEB1-dependent disruption of the mRNA translation program in oocytes during maternal aging

Nozomi Takahashi1,2,3, Federica Franciosi1,2,3,4, Enrico Maria Daldello1,2,3,5

  • 1Center for Reproductive Sciences, University of California, San Francisco, CA, 94143, USA.

Nature Communications
|January 25, 2023
PubMed

Insights

Aging impairs oocyte quality due to defective mRNA translation. Reduced cytoplasmic polyadenylation binding protein 1 (CPEB1) levels cause premature cell cycle activation, impacting fertility.

Area of Science:

  • Reproductive biology
  • Molecular and cellular biology
  • Aging research

Background:

  • Oocyte quality decline with age is a significant factor in female infertility.
  • Developmental competence of oocytes is critically dependent on post-transcriptional gene regulation.
  • The precise molecular mechanisms underlying age-related oocyte deterioration remain largely unknown.

Purpose of the Study:

  • To investigate the role of mRNA translation defects in the decline of oocyte quality during aging.
  • To identify specific molecular pathways involved in age-associated oocyte dysfunction.

Main Methods:

  • Analysis of ribosome loading on maternal transcripts in oocytes from young and old mice.
  • Assessment of mRNA translation using 3'-UTR-reporter assays.
  • Measurement of polyadenylation status of endogenous mRNAs.
  • Quantification of cytoplasmic polyadenylation binding protein 1 (CPEB1) mRNA and protein levels.
  • Functional rescue experiments involving CPEB1 mRNA injection.
  • Evaluation of oocyte-specific CPEB1 haploinsufficiency models.

Main Results:

  • A disruption in ribosome loading on maternal transcripts was observed in aged oocytes.
  • Altered translation of 3'-UTR-reporters and changes in poly(A) tail length of endogenous mRNAs were detected.
  • A significant decrease in CPEB1 mRNA translation and protein levels was found in aged oocytes.
  • Reduced CPEB1 led to de-repression of CCNB1 translation, premature CDK1 activation, and accelerated meiotic reentry.
  • CPEB1 mRNA injection corrected CCNB1 de-repression in aged oocytes.
  • Oocyte-specific CPEB1 haploinsufficiency in young oocytes mimicked the age-related translation defects.

Conclusions:

  • A functional defect in the oocyte translation program is a key contributor to the decline in oocyte quality during aging.
  • CPEB1 dysfunction plays a critical role in age-related oocyte aging by disrupting mRNA translation and cell cycle control.
  • These findings highlight mRNA translation as a potential therapeutic target for improving oocyte quality in aging females.

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