Chemotherapeutic agents are extensively used to treat malignancies. However, chemotherapy-induced ovarian damage and reduced fertility are severe side effects. Recently, stem cell transplantation has been reported to be an effective strategy for premature ovarian insufficiency (POI) treatment, but safety can still be an issue in stem cell-based therapy. Here, we show the protective effects of human umbilical cord mesenchymal stem cell-derived conditioned medium (hUCMSC-CM) on a cisplatin (Cs)-induced ovarian injury model. hUCMSC-CM can relieve Cs-induced depletion of follicles and preserve fertility. In addition, hUCMSC-CM can decrease apoptosis of oocytes and granulosa cells induced by Cs. RNA sequencing analysis reveals the differentially expressed genes of ovaries after Cs and hUCMSC-CM treatments, including genes involved in cell apoptosis. Furthermore, we show that the granulocyte colony-stimulating factor (G-CSF)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway plays an important role in protecting granulosa cells from Cs-induced apoptosis. Together, we confirm the protective effects of hUCMSC-CM on ovarian reserve and fertility in mice treated with Cs, highlighting the remarkable therapeutic effects of hUCMSC-CM.

中文翻译：

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人脐带间充质干细胞来源条件培养基对卵巢损伤的保护作用。

化学治疗剂广泛用于治疗恶性肿瘤。然而，化疗引起的卵巢损伤和生育能力下降是严重的副作用。最近，有报道称干细胞移植是治疗卵巢早衰（POI）的有效策略，但安全性仍然是基于干细胞的治疗的一个问题。在这里，我们展示了人脐带间充质干细胞衍生的条件培养基 (hUCMSC-CM) 对顺铂 (Cs) 诱导的卵巢损伤模型的保护作用。hUCMSC-CM 可以缓解 Cs 诱导的卵泡耗竭并保持生育能力。此外，hUCMSC-CM 可以减少 Cs 诱导的卵母细胞和颗粒细胞的凋亡。RNA测序分析揭示了Cs和hUCMSC-CM处理后卵巢的差异表达基因，包括参与细胞凋亡的基因。此外，我们表明粒细胞集落刺激因子 (G-CSF)/磷脂酰肌醇 3-激酶 (PI3K)/蛋白激酶 B (Akt) 通路在保护颗粒细胞免受 Cs 诱导的细胞凋亡方面起着重要作用。总之，我们证实了 hUCMSC-CM 对 Cs 治疗小鼠卵巢储备和生育能力的保护作用，突出了 hUCMSC-CM 的显着治疗效果。