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Enhancing Oocyte Quality in Aging Mice: Insights from Mesenchymal Stem Cell Therapy and FOXO3a Signaling Pathway Activation

  • Regenerative Medicine: Original Article
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Abstract

Ovarian aging reduced the quality of oocytes, resulting in age-related female infertility. It is reported that mesenchymal stem cells (MSCs) therapy can improve age-related ovarian function decline and the success rate of in vitro maturation (IVM) in assisted reproductive therapy. In order to investigate the effectiveness and mechanisms of MSCs to enhance oocyte quality of cumulus oocyte complexes (COCs) in advanced age, this study focus on the respective functional improvement of oocytes and granulosa cells (GCs) from aging mice and further to explore and verify the possible mechanisms. Here, we studied a popular but significant protein of follicular development, Forkhead box O-3a (FOXO3a), which is a transcription factor that mediates a variety of cellular processes, but the functions of which in regulating oocyte quality in MSCs therapy still remain inconclusive. In this study, the RNA-seq data of metaphase II (MII) oocytes and GCs isolated from COCs confirmed that, GCs of immature follicles show the most potential to be the targeted cells of bone marrow mesenchymal stem cells (BMSCs) by FOXO3a signaling pathway. Furthermore, we demonstrated the effectiveness of BMSCs co-culture with aging COCs to enhance oocyte quality and found its mechanism to function via ameliorating the biological function of GCs by alleviating FOXO3a levels. These results provide significant fundamental research on MSCs therapy on ovarian aging, as well as offering guidance for raising the success rate of assisted reproductive technology such IVM in clinical and non-clinical settings.

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Data Availability

The data for this study are available by contacting the corresponding author upon reasonable request.

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Acknowledgements

We thanks to all authors for their contribution to this experiment. We would also thank Genergy Biotechnology Co., Ltd. (Shanghai, China) for RNA high-throughput sequencing and bioinformatic analysis, as well as SANGON BIOTECH for designing and synthesis of various primers (shanghai, China) and RiboBio Co., Ltd. (Guangzhou, China) for the silencing sequence design and synthesis of target gene.

Funding

This work has been supported by the National Key Research and Development Program of China (2017YFC1002002) and the National Natural Science Foundation of China (82101700).

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Author notes

  1. Lingjuan Wang and Yang Liu These authors contributed equally to this work.

Authors and Affiliations

  1. Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    Lingjuan Wang, Qiaojuan Mei, Hongbei Mou, Huaibiao Li, Ling Zhang & Wenpei Xiang

  2. Department of Obstetrics and Gynecology Reproductive Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China

    Yang Liu

  3. National Clinical Research Center for Obstetrics and Gynecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    Lingjuan Wang, Yinhua Song, Jiachen Wu, Xinyu Tang, Jihui Ai & Kezhen Li

  4. Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    Lingjuan Wang, Yinhua Song & Jihui Ai

  5. Wuhan National High Magnetic Field Center, Huazhong University of Science and Technology, Wuhan, China

    Houxiu Xiao & Xiaotao Han

  6. Wuhan Kangjian Maternal and Infant Hospital, Wuhan, China

    Liqun Lv

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  1. Lingjuan Wang
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Contributions

Conceptualization: Ling Zhang, Wenpei Xiang.

Formal analysis: Lingjuan Wang, Yang Liu.

Methodology: Qiaojuan Mei, Hongbei Mou, Jiachen Wu, Xinyu Tang.

Project administration: Houxiu Xiao, Xiaotao Han, Liqun Lv, Huaibiao Li.

Resources: Jihui Ai, Kezhen Li.

Writing – original draft: Yinhua Song.

Writing – review & editing: Lingjuan Wang, Wenpei Xiang.

Corresponding authors

Correspondence to Ling Zhang or Wenpei Xiang.

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The application of specific pathogen-free grade C57BL/6 mice was approved by the Animal Ethics Committee of Huazhong University of Science and Technology and all experiments were carried out in accordance with relevant guidelines and regulations.

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Wang, L., Liu, Y., Song, Y. et al. Enhancing Oocyte Quality in Aging Mice: Insights from Mesenchymal Stem Cell Therapy and FOXO3a Signaling Pathway Activation. Reprod. Sci. (2024). https://doi.org/10.1007/s43032-024-01509-8

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