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Updated: Jul 24, 2025
Cell-Specific Paired Interrogation of the Mouse Ovarian Epigenome and Transcriptome
Published on: February 24, 2023
Multi-Omics Analysis Reveals Translational Landscapes and Regulations in Mouse and Human Oocyte Aging
Jiana Huang1,2,3, Peigen Chen1,2,3, Lei Jia1,2,3
1Reproductive Medicine Center, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510655, China.
Abstract:
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.
Insights
Maternal aging impairs oocyte quality due to decreased translational efficiency, linked to N6-methyladenosine (m6A) modification changes. Specific protein regulators like YTHDF3 in mice and SRSF6 in humans are key to controlling translation during oocyte aging.
Area of Science:
- Reproductive Biology
- Molecular Biology
- Genetics
Background:
- Maternal aging is characterized by abnormal meiosis and reduced oocyte quality.
- Translational control becomes critical during meiosis resumption in aging oocytes due to transcriptional silencing.
- Current understanding of aging-related translational mechanisms in oocytes is limited.
Purpose of the Study:
- To investigate the translatomics of oocyte aging in mice and humans.
- To identify molecular mechanisms regulating translation during oocyte aging.
- To uncover non-conservative regulators of translation control in meiosis resumption and maternal aging.
Main Methods:
- Multi-omics analysis of mouse oocytes.
- Analysis of N6-methyladenosine (m6A) modification and its associated proteins.
- Intervention studies involving YTHDF3 in mouse oocytes.
- Comparative analysis of translational landscapes in human oocytes.
Main Results:
- Aging in mouse oocytes shows decreased translational efficiency, linked to proteome changes and m6A modification.
- Reduced levels of m6A reader YTHDF3 inhibit oocyte meiotic maturation.
- YTHDF3 intervention affects the oocyte translatome and suppresses aging-associated factors.
- Human oocyte aging exhibits similar translational changes in epigenetic regulators, with SRSF6 playing a role independent of m6A.
Conclusions:
- The study profiles translational landscapes in aging mouse and human oocytes.
- Decreased translational efficiency and specific regulators like YTHDF3 (mice) and SRSF6 (humans) are crucial in oocyte aging.
- These findings reveal non-conservative regulators governing translation control during meiosis resumption and maternal aging.
