HucMSC-EVs Facilitate In Vitro Development of Maternally Aged Preantral Follicles and Oocytes
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Published:2023-03-02
Issue:5
Volume:19
Page:1427-1448
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ISSN:2629-3269
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Container-title:Stem Cell Reviews and Reports
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language:en
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Short-container-title:Stem Cell Rev and Rep
Author:
Zhang Ying-Yi, Yang Weijie, Zhang Yi, Hu Zhanhong, Chen Yingyan, Ma Yerong, Yang Anran, Shi Zhan, Zhou Hanjing, Ren Peipei, Shi Libing, Jin Jiamin, Rong Yan, Tong Xiaomei, Zhang Yin-Li, Zhang SongyingORCID
Abstract
AbstractFollicle developmental capacity and oocyte quality decline with advanced maternal age. Extracellular vesicles from human umbilical cord mesenchymal stem cells (HucMSC-EVs) act as a potential therapeutic product in the treatment of age-related ovarian dysfunction. In vitro culture (IVC) of preantral follicles is a useful method for understanding the mechanism of follicle development and is a promising means for improving female fertility. However, whether HucMSC-EVs have beneficial effects on aged follicle development during IVC has not yet been reported. Our research demonstrated that follicular development with single-addition withdrawal of HucMSC-EVs was better than that with continuous treatment with HucMSC-EVs. HucMSC-EVs facilitated the survival and growth of follicles, promoted the proliferation of granulosa cells (GCs), and improved the steroid hormone secretion of GCs during IVC of aged follicles. Both GCs and oocytes could uptake HucMSC-EVs. Moreover, we observed elevated cellular transcription in GCs and oocytes after treatment with HucMSC-EVs. The RNA sequencing (RNA-seq) results further validated that the differentially expressed genes are related to the promotion of GC proliferation, cell communication, and oocyte spindle organization. Additionally, the aged oocytes displayed a higher maturation rate, presented less aberrant spindle morphology, and expressed a higher level of the antioxidant protein Sirtuin 1 (SIRT1) after treatment with HucMSC-EVs. Our findings suggested that HucMSC-EVs can improve the growth and quality of aged follicles and oocytes in vitro through the regulation of gene transcription, which provides evidence for HucMSC-EVs as potential therapeutic reagents to restore female fertility with advanced age.
Graphical Abstract
Funder
National Key Research and Development Program of China Key Projects Jointly Constructed by the Ministry and the Province of Zhejiang Medical and Health Science and Technology Project National Natural Science Foundation of China
Publisher
Springer Science and Business Media LLC
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