Conditioned media and extracellular vesicles derived from human Wharton’s jelly mesenchymal stem cells improve the in vitro maturation of immature oocytes in normal and PCOS mouse model

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BACKGROUND: The effects of conditioned medium (CM) and extracellular vesicles (EVs) derived from human Wharton's jelly mesenchymal stem cells (hWJMSCs) on in vitro maturation (IVM) of immature oocytes in both normal and polycystic ovary syndrome (PCOS)-induced mice were investigated. PCOS was induced in adult female NMRI mice by administering letrozole (90 μg/kg/day) via gavage for one week. Germinal vesicle (GV) oocytes were collected from both PCOS-induced and normal mice, while mature oocytes (MII) were obtained from superovulated normal mice to serve as controls. The experimental groups included 7 groups: Control (MII oocytes), 3 IVM groups (in vitro maturation of GV oocytes): IVM (with simple IVM media), IVM + CM, and IVM + EVs (IVM media supplemented with CM and EVs, respectively), and three PCOS groups (in vitro maturation of GV oocytes from PCOS-induced mice): PCOS IVM (with simple IVM media), PCOS IVM + CM, and PCOS IVM + EVs (IVM media supplemented with CM and EVs, respectively). After IVM was conducted in all groups, mature oocytes were harvested and assessed for maturation rate, morphology, viability, and gene expression profiles of key regulators (CDK1, CCNB1, MAP2K). Developmentally competent oocytes were selected using Brilliant Cresyl Blue staining and then subjected to in vitro maturation with or without CM or EVs supplementation. Nuclear maturation was evaluated via orcein staining, while viability was assessed using Trypan Blue. Morphometric parameters were measured using ImageJ software. Real-time PCR was utilized for the evaluation of gene expression of targeted genes. RESULTS: Results demonstrated that in BCB + oocytes, CM and EVs improved the mature oocytes compared to IVM. Oocytes from PCOS-induced mice exhibited reduced maturation and increased degeneration, which were rescued by CM and EV treatment. Gene expression analysis revealed downregulation of MAP2K, CCNB1, and CDK1 in IVM and PCOS IVM groups compared to the control group, while CM supplementation restored their expression. Oocyte diameter and viability were significantly enhanced in IVM + CM compared to IVM (P < 0.05). CONCLUSIONS: These findings suggest that hWJMSC-derived secretomes, particularly CM, enhance oocyte maturation and quality, offering potential therapeutic benefits for IVM in both normal and PCOS conditions.

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