Human Placental Stem Cells Derived Exosomes Xenograft Recover Ovarian Function in Training-induced Premature Ovarian Insufficiency Rats

Background: Mesenchymal stem cells (MSCs) were able to restore ovarian function in premature ovarian insufficiency (POI), which can be largely attributed to the paracrine effects of MSCs therapy. However, the function and mechanism of MSC-derived exosomes transplantation for POI are not fully understood. Objective: To investigate the efficacy and underlying mechanisms of human placental derived MSCs derived exosomes (hpMSC-Exos) xenotransplantation in incremental load training-induced POI. Method: The incremental exercise treadmill training was employed for constructing the POI rat model. hpMSC-Exos were administered to POI rats by tail vein injection. The ovarian function was assessed based on histological analysis and hormone levels. Ovarian function parameters, follicle counts, oocyte aging, granulosa cell apoptosis, and follicular microenvironment were evaluated. Results: The tracking of hpMSC-Exos indicated that they generally colonized the ovarian tissues. hpMSC-Exos transplantation increased telomere length and telomerase activity, reduced oxidative stress, downregulated the Bax and caspase-3 gene expression, upregulated the Bcl-2 gene expression, and increased the insulin-like growth factor 1 (Igf-1) and vascular endothelial growth factor (VEGF) expression level. Furthermore, the findings showed that the follicle-stimulating hormone (FSH) level and FSH to luteinizing hormone (LH) ratio were decreased, whereas the population of follicles significantly increased after transplantation. Conclusion: hpMSC-Exos transplantation was observed to improve the function of the injured ovarian tissues in the incremental load training-induced POI rats. Furthermore, the mechanisms of hpMSC-Exos are related to delaying aging in the oocyte, reducing apoptosis of granulosa cells, and regulating the follicular microenvironment.