ORCID

0000-0002-9014-132X (Brachova), 0000-0003-4067-4387 (Alvarez)

Document Type

Article

Publication Date

2025

DOI

10.3390/ijms26199395

Publication Title

International Journal of Molecular Sciences

Volume

26

Issue

19

Pages

9395 (1-16)

Abstract

Oocytes from women of advanced reproductive age exhibit diminished developmental potential, but the underlying mechanisms remain incompletely defined. Oocyte maturation depends on translational control of maternal mRNA synthesized during growth. We performed a computational analysis on human oocytes from women < 30 versus ≥40 years and observed that mRNA GC content correlates negatively with half-life in oocytes from young (< 30 yr) but positively with oocytes from aged (>40 yr) women. In young oocytes, longer mRNA half-life is associated with lower protein abundance, whereas in aged oocytes GC content correlates positively with protein abundance. During the GV-to-MII transition, codon composition stratifies stability: codons that support rapid translation (optimal) stabilize mRNA, while slow-translating codons (non-optimal) promote decay. With reproductive aging, GC-containing codons become more optimal and align with increased protein abundance. These findings indicate that reproductive aging remodels codon-optimality-linked, translation-coupled mRNA decay, stabilizing a subset of GC-rich maternal mRNA that may be prone to excess translation during maturation. Our analysis is explicitly within human reproductive aging; it does not revisit cross-species stability rules. Instead, it shows that sequence–stability relations are reprogrammed with age within human oocytes, including an inversion of the GC–stability association during GV-to-MII transition. Disruption of the normal mRNA clearance program in aged oocytes may compromise oocyte competence and alter maternal mRNA dosage, with downstream consequences for early embryonic development.

Rights

© 2025 by the authors.

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International (CC BY 4.0) License.

Data Availability

Data availability statement: "All datasets analyzed in this study were previously published and are publicly available. The human oocyte RNA-seq data are deposited in the NCBI Sequence Read Archive (SRA) under BioProject PRJNA377237 [36], and the proteomics data used for GV-to-MII protein quantification are available via the ProteomeXchange Consortium under accession PXD003691 [40]. Reference resources (GENCODE v34 transcript annotations and the human UniProt proteome) are described in Methods."

Original Publication Citation

Brachova, P., Christenson, L. K., & Alvarez, N. S. (2025). Codon composition in human oocytes reveals age-associated defects in mRNA decay. International Journal of Molecular Sciences, 26(19), 1-16, Article 9395. https://doi.org/10.3390/ijms26199395

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