Human umbilical cord mesenchymal stem cell‑derived exosomes improve ovarian function in natural aging by inhibiting apoptosis

Li,Zhongkang; Li,Zhongkang; Liu,Yibin; Liu,Yibin; Tian,Yanpeng; Tian,Yanpeng; Li,Qian; Li,Qian; Shi,Wenxin; Shi,Wenxin; Zhang,Jingkun; Zhang,Jingkun; Zhang,Huihui; Zhang,Huihui; Tan,Yi; Tan,Yi; Yang,Shuangshuang; Yang,Shuangshuang; Yang,Tao; Yang,Tao; Huang,Xianghua; Huang,Xianghua; Du,Yanfang; Du,Yanfang

doi:10.3892/ijmm.2023.5297

Human umbilical cord mesenchymal stem cell‑derived exosomes improve ovarian function in natural aging by inhibiting apoptosis

Authors:
- Zhongkang Li
- Yibin Liu
- Yanpeng Tian
- Qian Li
- Wenxin Shi
- Jingkun Zhang
- Huihui Zhang
- Yi Tan
- Shuangshuang Yang
- Tao Yang
- Xianghua Huang
- Yanfang Du
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Affiliations: Department of Obstetrics and Gynecology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China, Department of Obstetrics and Gynecology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China, R&D Department, Shandong Qilu Cell Therapy Engineering Technology Co., Ltd., Jinan, Shandong 25000, P.R. China, Department of Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China
Published online on: August 23, 2023 https://doi.org/10.3892/ijmm.2023.5297
Article Number: 94
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Prolonging the reproductive lifespan is beneficial for preserving the physical and psychological health of women. The transplantation of mesenchymal stem cell (MSC)‑derived exosomes (MSC‑Exos) has been reported to be a promising regenerative therapeutic strategy for restoring the function of aging ovaries. The present study thus evaluated the therapeutic efficacy of exosomes derived from human umbilical cord‑MSCs (hUCMSC‑Exos) in a mouse model of natural ovarian aging (NOA), and further investigated the role of exosomal microRNAs (miRNAs/miRs) in the mechanisms of this creative therapy. Specifically, following the administration of hUCMSC‑Exos in mice with NOA, ovarian function was found to improve, as indicated by the restoration of follicle numbers and hormone levels. These exosomes were found to exhibit the ability to inhibit PTEN expression and suppress apoptosis both in vivo and in vitro. Subsequently, miRNA sequencing of the exosomes was performed, following which bioinformatics analysis was used to identify the highly expressed miRNAs that are capable of targeting PTEN expression. Through high‑throughput sequencing and molecular analyses, miR‑21‑5p was found to be the highest in ranking in terms of expression, suggesting that hUCMSC‑Exos can preserve ovarian function by suppressing PTEN expression to inhibit apoptosis by delivering miR‑21‑5p. On the whole, the results of the present study suggest that the application of exosomes can be used to restore ovarian function in mice with NOA. These positive findings also suggest that the transplantation of exosomes derived from MSCs holds promise as an agent against ovarian aging.

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