Codon Composition in Human Oocytes Reveals Age-Associated Defects in mRNA Decay

Area of Science:

• Reproductive Biology
• Molecular Biology
• Genetics

Background:

• Oocyte developmental potential declines with advanced reproductive age.
• Mechanisms underlying age-related oocyte dysfunction are not fully understood.
• Oocyte maturation relies on translational control of maternal mRNA.

Purpose of the Study:

• To investigate how maternal mRNA stability and translation are affected by reproductive aging in human oocytes.
• To identify age-dependent changes in mRNA sequence-stability relationships.
• To explore the impact of these changes on oocyte competence and early embryonic development.

Main Methods:

• Computational analysis of human oocytes from women aged <30 years versus ≥40 years.
• Examination of mRNA GC content, half-life, and protein abundance.
• Analysis of codon composition and its effect on mRNA stability during oocyte maturation (GV-to-MII transition).

Main Results:

• mRNA GC content inversely correlates with half-life in young oocytes but positively correlates in aged oocytes.
• In aged oocytes, GC content positively correlates with protein abundance.
• Reproductive aging alters codon optimality, favoring GC-rich codons and stabilizing specific maternal mRNAs.
• An inversion of the GC-stability association occurs during the GV-to-MII transition with age.

Conclusions:

• Reproductive aging reprograms translation-coupled mRNA decay pathways in human oocytes.
• Aged oocytes may stabilize GC-rich maternal mRNAs, leading to potential over-translation during maturation.
• Disrupted mRNA clearance in aged oocytes can compromise oocyte competence and affect maternal mRNA dosage, impacting embryonic development.