Translational studies have explored the therapeutic potential and feasibility of mesenchymal stem cells (MSCs) in several degenerative diseases; however, mechanistic studies of the function of these cells have been insufficient. As ovarian failure causes anovulation as well as ovarian steroid hormonal imbalances, the specific aims of this study were to analyze the therapeutic role of placenta-derived MSCs (PD-MSCs) in an ovarian failure ovariectomy (OVX) rat model and evaluate whether PD-MSC transplantation (Tx) improved folliculogenesis and oocyte maturation in the injured ovary through PI3K/Akt and FOXO signaling. Blood and ovary tissue were collected and analyzed after various PD-MSC Tx treatments in an ovariectomized rat model. Changes in the expression of folliculogenesis- and ovary regeneration-related genes induced by PD-MSC treatments were analyzed by qRT-PCR, Western blotting, and histological analysis. The levels of hormones related to ovary function were significantly increased in the PD-MSC Tx groups compared with those in the nontransplantation group (NTx). The follicle numbers in the ovarian tissues were increased along with the increased expression of genes related to folliculogenesis in the PD-MSC Tx groups compared with the NTx groups. Furthermore, Tx PD-MSCs induced follicle maturation by increasing the phosphorylation of GSK3 beta and FOXO3 (p < 0.05) and shifting the balance of growth and apoptosis in oocytes. Taken together, these results show that PD-MSC Tx can restore ovarian function and induce ovarian folliculogenesis via the PI3K/Akt and FOXO signaling pathway.

中文翻译：

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胎盘来源的间充质干细胞诱导的微环境变化通过激活 PI3K-FOXO3 通路恢复去卵巢大鼠的卵巢功能

转化研究探索了间充质干细胞 (MSCs) 在几种退行性疾病中的治疗潜力和可行性；然而，对这些细胞功能的机制研究还不够。由于卵巢衰竭导致无排卵以及卵巢类固醇激素失衡，本研究的具体目的是分析胎盘来源的 MSCs (PD-MSCs) 在卵巢衰竭卵巢切除术 (OVX) 大鼠模型中的治疗作用，并评估 PD- MSC 移植 (Tx) 通过 PI3K/Akt 和 FOXO 信号传导改善受损卵巢中的卵泡发生和卵母细胞成熟。在卵巢切除大鼠模型中，在各种 PD-MSC Tx 治疗后收集和分析血液和卵巢组织。通过 qRT-PCR、蛋白质印迹和组织学分析分析了 PD-MSC 治疗诱导的卵泡发生和卵巢再生相关基因表达的变化。与非移植组 (NTx) 相比，PD-MSC Tx 组与卵巢功能相关的激素水平显着增加。与 NTx 组相比，PD-MSC Tx 组卵巢组织中的卵泡数量随着与卵泡发生相关基因表达的增加而增加。此外，Tx PD-MSCs 通过增加 GSK3 β 和 FOXO3 的磷酸化 (p < 0.05) 并改变卵母细胞的生长和凋亡平衡来诱导卵泡成熟。综合起来，