Age‐related differences in the translational landscape of mammalian oocytes

Llano, Edgar Del; Mašek, Tomáš; Gahurová, Lenka; Pospíšek, Martin; Končická, Markéta; Jindrova, Anna; Jansová, Denisa; Iyyappan, Rajan; Roučová, Kristina; Bruce, Alexander W.; Kubelka, Michal; Šušor, Andrej

doi:10.1111/acel.13231

Cited by 14 publications

(22 citation statements)

References 54 publications

(104 reference statements)

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“…This could suggest that abnormal protein levels of chromosomal factors in aged oocytes might trigger compensatory mechanisms including increased polyadenylation of those transcripts for further translation. In support of this hypothesis, a recent study profiling the translatome of ageing mouse oocytes identified transcripts related to meiotic spindle formation and chromosome alignment as misregulated during translation (del Llano et al, 2020).…”

Section: Discussionmentioning

confidence: 91%

“…shown that altered translation of specific transcripts is a contributing factor to the age-related quality decline in mouse oocytes (del Llano et al, 2020). Further studies will be needed to assess the role of CPEB2 in human oocytes.…”

Section: Transcripts Affected By Age Are Related To Oxidative Stress Mitochondrial Function Chromosome Segregation and Rna Metabolism Patmentioning

confidence: 99%

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Single human oocyte transcriptome analysis reveals distinct maturation stage‐dependent pathways impacted by age

Llonch

Barragán²,

Nieto

et al. 2021

Aging Cell

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Section: Discussionmentioning

confidence: 91%

Section: Transcripts Affected By Age Are Related To Oxidative Stress Mitochondrial Function Chromosome Segregation and Rna Metabolism Patmentioning

confidence: 99%

Single human oocyte transcriptome analysis reveals distinct maturation stage‐dependent pathways impacted by age

Llonch

Barragán²,

Nieto

et al. 2021

Aging Cell

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“…Whether or not these transcripts are similarly translated during reproductive aging remains to be determined. Recent work in mice has shown that reproductive aging in oocytes is associated with increased ribosome synthesis (Duncan et al 2017) and altered mRNA translation (Llano et al 2020). It is conceivable that human reproductive aging follows similar aging-related dysregulation, in which there is enhancement of the established mRNA decay programs.…”

Section: Gc Content Reveals Differential Correlations Between Mrna Hamentioning

confidence: 99%

“…4d, ⍴ = 0.39, p < 0.05).The correlation between the PACC and the reproductive aging CSC suggest that a subset of mRNA could be potentially stabilized and translated over a longer period of time during oocyte maturation. This phenomenon is called over-translation and has been observed in mice models for defects in translational mRNA decay (Sha et al 2018) as well as reproductively aged oocytes (Llano et al 2020).…”

Section: Age Associated Changes In Codon Optimalitymentioning

confidence: 99%

“…Aneuploidy is a defining feature associated with reproductive aging in oocytes (Sandalinas et al 2002; Mai et al 2013; Treff et al 2016). Mouse models for reproductive aging have indicated defective translation of meiotic regulators in the oocytes from aged mice, which is hypothesized to drive aneuploidy (Duncan et al 2017; Llano et al 2020). The underlying cause of age-associated translational dysregulation remains to be determined in oocytes.…”

Section: Introductionmentioning

confidence: 99%

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Codon composition in human oocytes reveals age-associated defects in mRNA decay

Alvarez

Brachova

Christenson

2021

Preprint

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Oocytes from women of advanced reproductive age have lower developmental potential, yet the underlying mechanisms of this phenomena are incompletely understood. Oocyte maturation is dependent upon translational control of stored maternal mRNA that were synthesized during oocyte growth. We observed that GC content of mRNA was negatively associated with half-life in oocytes from reproductively young women (< 30 years), contrastingly directly with oocytes from reproductively aged women (≥ 40 years) where mRNA half-lives were positively associated with GC nucleotide content. Additionally, we observed that mRNA half-lives were negatively associated with protein abundance in young oocytes, while GC content was positively associated with protein abundance in aged oocytes. Examination of codon composition during the GV-to-MII transition revealed that codons that facilitate rapid translation promoted mRNA stability and are considered optimal, while codons that slow translation destabilized mRNA, and are considered non-optimal. GC-containing codons were more optimal in reproductive aging, and also correlated positively with protein abundance. This study indicates that reproductive aging coincides with the stabilization of a subset of mRNA that have the potential to be over-translated during oocyte maturation, this is likely to lead to observed decreases in oocyte quality in older women. Because oocyte mRNA decay is translationally linked, this suggests that maternal aging causes defects in translation, which results in reduced translational efficiency and the retention of maternal mRNA that are normally degraded in oocytes from young women. In the case of oocytes, defects in translation can alter the RNA decay pathways and result in incorrect maternal mRNA dosage, which may negatively impact embryonic development.

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Multi‐Omics Analysis Reveals Translational Landscapes and Regulations in Mouse and Human Oocyte Aging

Huang

Chen

et al. 2023

Advanced Science

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Abnormal resumption of meiosis and decreased oocyte quality are hallmarks of maternal aging. Transcriptional silencing makes translational control an urgent task during meiosis resumption in maternal aging. However, insights into aging‐related translational characteristics and underlying mechanisms are limited. Here, using multi‐omics analysis of oocytes, it is found that translatomics during aging is related to changes in the proteome and reveals decreased translational efficiency with aging phenotypes in mouse oocytes. Translational efficiency decrease is associated with the N6‐methyladenosine (m6A) modification of transcripts. It is further clarified that m6A reader YTHDF3 is significantly decreased in aged oocytes, inhibiting oocyte meiotic maturation. YTHDF3 intervention perturbs the translatome of oocytes and suppress the translational efficiency of aging‐associated maternal factors, such as Hells, to affect the oocyte maturation. Moreover, the translational landscape is profiled in human oocyte aging, and the similar translational changes of epigenetic modifications regulators between human and mice oocyte aging are observed. In particular, due to the translational silence of YTHDF3 in human oocytes, translation activity is not associated with m6A modification, but alternative splicing factor SRSF6. Together, the findings profile the specific translational landscapes during oocyte aging in mice and humans, and uncover non‐conservative regulators on translation control in meiosis resumption and maternal aging.

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Age‐related differences in the translational landscape of mammalian oocytes

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 14 publications

References 54 publications

Single human oocyte transcriptome analysis reveals distinct maturation stage‐dependent pathways impacted by age

Single human oocyte transcriptome analysis reveals distinct maturation stage‐dependent pathways impacted by age

Codon composition in human oocytes reveals age-associated defects in mRNA decay

Multi‐Omics Analysis Reveals Translational Landscapes and Regulations in Mouse and Human Oocyte Aging

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