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.

人脐带间充质干细胞（UC-MSC）的应用是治疗卵巢早衰（POF）的一种有前途的治疗方法。但是，关于人脐带MSC（UC-MSC）对化学疗法诱发的卵巢损伤的炎症调节作用，无论在体内还是体外均知之甚少。这项研究旨在调查UC-MSC移植的治疗效果以及有关POF小鼠凋亡和炎症的潜在机制。腹腔内注射环磷酰胺可诱导化疗诱导的POF模型。检查卵巢功能参数，颗粒细胞（GC）凋亡和炎症。形态学染色显示，UC-MSC处理可增加卵巢大小，并增加初级和次级卵泡的数量，但减少了卵泡的卵泡数目。与POF组相比，UC-MSC治疗组的雌二醇水平升高，而促卵泡激素水平降低。UC-MSCs抑制环磷酰胺诱导的GC凋亡和炎症。同时，UC-MSC处理后AKT和P38的磷酸化升高。体内对UC-MSC的追踪表明，移植的UC-MSC仅位于卵巢间质而不是卵泡中。重要的是，源自UC-MSC的细胞外囊泡可保护GC免受烷基化剂诱导的细胞凋亡和体外炎症。我们的研究结果表明，UC-MSC移植可通过旁分泌机制通过抗凋亡和抗炎作用，减轻化疗诱导的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升高，而促卵泡激素水平降低。UC-MSCs抑制环磷酰胺诱导的GC凋亡和炎症。同时，UC-MSC处理后AKT和P38的磷酸化升高。体内对UC-MSC的追踪表明，移植的UC-MSC仅位于卵巢间质而不是卵泡中。重要的是，源自UC-MSC的细胞外囊泡可保护GC免受烷基化剂诱导的细胞凋亡和体外炎症。我们的研究结果表明，UC-MSC移植可通过旁分泌机制通过抗凋亡和抗炎作用，减轻化疗诱导的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升高，而促卵泡激素水平降低。UC-MSCs抑制环磷酰胺诱导的GC凋亡和炎症。同时，UC-MSC处理后AKT和P38的磷酸化升高。体内对UC-MSC的追踪表明，移植的UC-MSC仅位于卵巢间质而不是卵泡中。重要的是，源自UC-MSC的细胞外囊泡可保护GC免于烷基化剂诱导的细胞凋亡和体外炎症。我们的研究结果表明，UC-MSC移植可通过旁分泌机制通过抗凋亡和抗炎作用，减轻化疗诱导的POF小鼠的卵巢损伤并改善卵巢功能。