Human umbilical cord mesenchymal stem cell (UC-MSC) application is a promising arising therapy for the treatment of premature ovarian failure (POF). However, little is known about the inflammation regulatory effects of human umbilical cord MSCs (UC-MSCs) on chemotherapy-induced ovarian damage, regardless of in vivo or in vitro. This study was designed to investigate the therapeutic effects of UC-MSC transplantation and underlying mechanisms regarding both apoptosis and inflammation in POF mice. The chemotherapy-induced POF models were induced by intraperitoneal injection of cyclophosphamide. Ovarian function parameters, granulosa cell (GC) apoptosis, and inflammation were examined. Morphological staining showed that UC-MSC treatment increased the ovary size, and the numbers of primary and secondary follicles, but decreased the number of atretic follicles. Estradiol levels in the UC-MSC-treated group were increased while follicle-stimulating hormone levels were reduced compared to those in the POF group. UC-MSCs inhibited cyclophosphamide-induced GC apoptosis and inflammation. Meanwhile, phosphorylation of AKT and P38 was elevated after UC-MSC treatment. Tracking of UC-MSCs in vivo indicated that transplanted UC-MSCs were only located in the interstitium of ovaries rather than in follicles. Importantly, UC-MSC-derived extracellular vesicles protected GCs from alkylating agent-induced apoptosis and inflammation in vitro. Our results suggest that UC-MSC transplantation can reduce ovary injury and improve ovarian function in chemotherapy-induced POF mice through anti-apoptotic and anti-inflammatory effects via a paracrine mechanism.

中文翻译：

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人脐带间充质干细胞通过旁分泌机制抑制细胞凋亡和炎症，改善化疗诱导的卵巢早衰小鼠的卵巢功能。

人脐带间充质干细胞 (UC-MSC) 的应用是一种很有前景的治疗卵巢早衰 (POF) 的疗法。然而，关于人脐带间充质干细胞 (UC-MSCs) 在体内或体外对化疗引起的卵巢损伤的炎症调节作用知之甚少。本研究旨在研究 UC-MSC 移植的治疗效果以及 POF 小鼠细胞凋亡和炎症的潜在机制。通过腹腔注射环磷酰胺诱导化疗诱导的POF模型。检查了卵巢功能参数、颗粒细胞 (GC) 细胞凋亡和炎症。形态学染色显示 UC-MSC 处理增加了卵巢大小，以及初级和次级卵泡的数量，但减少了闭锁卵泡的数量。与 POF 组相比，UC-MSC 治疗组的雌二醇水平增加，而促卵泡激素水平降低。UC-MSCs 抑制环磷酰胺诱导的 GC 细胞凋亡和炎症。同时，UC-MSC 治疗后 AKT 和 P38 的磷酸化升高。体内追踪UC-MSCs表明移植的UC-MSCs仅位于卵巢间质而不是卵泡中。重要的是，UC-MSC 衍生的细胞外囊泡在体外保护 GC 免受烷化剂诱导的细胞凋亡和炎症。我们的结果表明，UC-MSC 移植可以通过旁分泌机制的抗凋亡和抗炎作用减少化疗诱导的 POF 小鼠的卵巢损伤并改善卵巢功能。与 POF 组相比，UC-MSC 治疗组的雌二醇水平增加，而促卵泡激素水平降低。UC-MSCs 抑制环磷酰胺诱导的 GC 细胞凋亡和炎症。同时，UC-MSC 治疗后 AKT 和 P38 的磷酸化升高。体内追踪UC-MSCs表明移植的UC-MSCs仅位于卵巢间质而不是卵泡中。重要的是，UC-MSC 衍生的细胞外囊泡在体外保护 GC 免受烷化剂诱导的细胞凋亡和炎症。我们的结果表明，UC-MSC 移植可以通过旁分泌机制的抗凋亡和抗炎作用减少化疗诱导的 POF 小鼠的卵巢损伤并改善卵巢功能。与 POF 组相比，UC-MSC 治疗组的雌二醇水平增加，而促卵泡激素水平降低。UC-MSCs 抑制环磷酰胺诱导的 GC 细胞凋亡和炎症。同时，UC-MSC 治疗后 AKT 和 P38 的磷酸化升高。体内追踪UC-MSCs表明移植的UC-MSCs仅位于卵巢间质而不是卵泡中。重要的是，UC-MSC 衍生的细胞外囊泡在体外保护 GC 免受烷化剂诱导的细胞凋亡和炎症。我们的结果表明，UC-MSC 移植可以通过旁分泌机制的抗凋亡和抗炎作用减少化疗诱导的 POF 小鼠的卵巢损伤并改善卵巢功能。