https://doi.org/10.4081/ejh.2023.3506

Therapeutic effects of human umbilical cord mesenchymal stem cell-derived extracellular vesicles on ovarian functions through the PI3K/Akt cascade in mice with premature ovarian failure

Vol. 67 No. 3 (2023)
Submitted: 28 July 2022
Accepted: 28 December 2022
Published: 27 July 2023
Premature ovarian failure, human umbilical cord mesenchymal stem cells, extracellular vesicles, PI3K/Akt, therapeutic effects, D-galactose
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Authors

Nan Li
Department of Gynecological Ward, The Third Affiliated Hospital, Jinzhou Medical University, Jinzhou, China.
Xue Fan
XueFan0520@163.com
Department of Gynecological Ward, The Third Affiliated Hospital, Jinzhou Medical University, Jinzhou, China.
Lihong Liu
Department of Gynecological Ward, The Third Affiliated Hospital, Jinzhou Medical University, Jinzhou, China.
Yanbing Liu
Department of Gynecological Ward, The Third Affiliated Hospital, Jinzhou Medical University, Jinzhou, China.

Premature ovarian failure (POF) mainly refers to ovarian dysfunction in females younger than forty. Mesenchymal stem cells (MSCs) are considered an increasingly promising therapy for POF. This study intended to uncover the therapeutic effects of human umbilical cord MSC-derived extracellular vesicles (hucMSCEVs) on POF. hucMSCs were identified by observing morphology and examining differentiation capabilities. EVs were extracted from hucMSCs and later identified utilizing nanoparticle tracking analysis, transmission electron microscopy, and Western blotting. POF mouse models were established by injecting D-galactose (Dgal). The estrous cycles were assessed through vaginal cytology, and serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), anti-mullerian hormone (AMH), estradiol (E2), and progesterone (P) were measured by ELISA. The human ovarian granulosa cell line KGN was used for in vitro experiments. The uptake of hucMSC-EVs by KGN cells was detected. After D-gal treatment, cell proliferation and apoptosis were assessed via CCK-8 assay and flow cytometry. The PI3K/Akt pathway-related proteins were determined by Western blotting. Our results revealed that POF mice had prolonged estrous cycles, increased FSH and LH levels, and decreased AMH, E2, and P levels. Treatment with hucMSC-EVs partially counteracted the above changes. D-gal treatment reduced proliferation and raised apoptosis in KGN cells, while hucMSC-EV treatment annulled the changes. D-gal-treated cells exhibited downregulated p-PI3K/PI3K and p-Akt/Akt levels, while hucMSC-EVs activated the PI3K/Akt pathway. LY294002 suppressed the roles of hucMSC-EVs in promoting KGN cell proliferation and lowering apoptosis. Collectively, hucMSC-EVs facilitate proliferation and suppress apoptosis of ovarian granulosa cells by activating the PI3K/Akt pathway, thereby alleviating POF.

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Ethics Approval

Animal experiments were ratified by the Ethics Committee of The Third Affiliated Hospital, Jinzhou Medical University (JZ2021023)

How to Cite

Li, N., Fan, X., Liu, L., & Liu, Y. (2023). Therapeutic effects of human umbilical cord mesenchymal stem cell-derived extracellular vesicles on ovarian functions through the PI3K/Akt cascade in mice with premature ovarian failure. European Journal of Histochemistry, 67(3). https://doi.org/10.4081/ejh.2023.3506
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