Abstract：
BACKGROUND: Premature ovarian failure (POF), also known as primary ovarian insufficiency, is a common endocrine disease in young women. The emergence of regenerative medicine using stem cells may improve ovarian function and structure, and represents a promising prospect for POF treatment. In his study, we explored the therapeutic effects of human umbilical cord mesenchymal stem cell (HUCMSC) transplantation in a Tibetan miniature pig model of cyclophosphamide (CTX)-induced POF.
METHODS: We cultured and identified HUCMSCs, labeled them with DiR iodide red dye, and implanted them into a CTX-induced model of POF in Tibetan miniature pigs. The daily weight changes were recorded, and the levels of estradiol (E2) and follicle-stimulating hormone (FSH) were measured on days 0, 7, and 14. At the end of the 21-day observation period, in vivo imaging of the bilateral ovaries was performed, and the ovarian index was measured. Ovarian tissue morphology and follicles were examined by hematoxylin-eosin staining. The terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay was employed to assess cell apoptosis, and immunohistochemistry was used to determine the levels of p-AKT, p-ERK1/2, BAX, and BCL2 expression.
RESULTS: Our analysis indicated successful delivery of HUCMSCs to the ovaries of the POF pig model. Significant increases were observed in body weight, E2 levels, ovarian index, and number of normal follicles (all p < 0.05). Moreover, FSH levels reduced and ovarian tissue morphology improved following HUCMSCs transplantation (all p < 0.05). Importantly, upregulated p-AKT, p-ERK1/2, and BCL2 expression were observed, whereas the expression of BAX was suppressed (all p < 0.05), suggesting the inhibition of ovarian cell apoptosis.
CONCLUSIONS: Our study highlights the significant therapeutic effects of HUCMSC transplantation on CTX-induced POF in a Tibetan miniature pig model.
METHODS: We cultured and identified HUCMSCs, labeled them with DiR iodide red dye, and implanted them into a CTX-induced model of POF in Tibetan miniature pigs. The daily weight changes were recorded, and the levels of estradiol (E2) and follicle-stimulating hormone (FSH) were measured on days 0, 7, and 14. At the end of the 21-day observation period, in vivo imaging of the bilateral ovaries was performed, and the ovarian index was measured. Ovarian tissue morphology and follicles were examined by hematoxylin-eosin staining. The terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay was employed to assess cell apoptosis, and immunohistochemistry was used to determine the levels of p-AKT, p-ERK1/2, BAX, and BCL2 expression.
RESULTS: Our analysis indicated successful delivery of HUCMSCs to the ovaries of the POF pig model. Significant increases were observed in body weight, E2 levels, ovarian index, and number of normal follicles (all p < 0.05). Moreover, FSH levels reduced and ovarian tissue morphology improved following HUCMSCs transplantation (all p < 0.05). Importantly, upregulated p-AKT, p-ERK1/2, and BCL2 expression were observed, whereas the expression of BAX was suppressed (all p < 0.05), suggesting the inhibition of ovarian cell apoptosis.
CONCLUSIONS: Our study highlights the significant therapeutic effects of HUCMSC transplantation on CTX-induced POF in a Tibetan miniature pig model.
摘要：
背景：卵巢早衰（POF），也被称为原发性卵巢功能不全，是年轻女性常见的内分泌疾病。使用干细胞的再生医学的出现可能会改善卵巢功能和结构，代表了POF治疗的前景。在他的书房里,我们探讨了人脐带间充质干细胞（HUCMSC）移植在藏族小型猪环磷酰胺（CTX）诱导的POF模型中的治疗作用。
方法：我们培养并鉴定了HUCMSCs，用DiR碘化物红色染料标记它们，并将它们植入CTX诱导的西藏小型猪POF模型中。记录每日体重变化，在第0、7和14天测量雌二醇（E2）和促卵泡激素（FSH）的水平。在21天观察期结束时，对双侧卵巢进行了体内成像,测量卵巢指数。通过苏木精-伊红染色检查卵巢组织形态和卵泡。末端脱氧核苷酸转移酶介导的dUTP缺口末端标记试验用于评估细胞凋亡，免疫组织化学用于确定p-AKT的水平，p-ERK1/2,BAX,和BCL2表达式。
结果:我们的分析表明HUCMSC成功递送至POF猪模型的卵巢。观察到体重显着增加，E2级别,卵巢指数,正常卵泡数(均p<0.05)。此外，HUCMSCs移植后FSH水平降低，卵巢组织形态改善（均p<0.05）。重要的是,上调p-AKT,观察到p-ERK1/2和BCL2的表达，而BAX的表达被抑制（所有p<0.05），提示抑制卵巢细胞凋亡。
结论：我们的研究强调了HUCMSC移植对西藏小型猪模型中CTX诱导的POF的显著治疗效果。
方法：我们培养并鉴定了HUCMSCs，用DiR碘化物红色染料标记它们，并将它们植入CTX诱导的西藏小型猪POF模型中。记录每日体重变化，在第0、7和14天测量雌二醇（E2）和促卵泡激素（FSH）的水平。在21天观察期结束时，对双侧卵巢进行了体内成像,测量卵巢指数。通过苏木精-伊红染色检查卵巢组织形态和卵泡。末端脱氧核苷酸转移酶介导的dUTP缺口末端标记试验用于评估细胞凋亡，免疫组织化学用于确定p-AKT的水平，p-ERK1/2,BAX,和BCL2表达式。
结果:我们的分析表明HUCMSC成功递送至POF猪模型的卵巢。观察到体重显着增加，E2级别,卵巢指数,正常卵泡数(均p<0.05)。此外，HUCMSCs移植后FSH水平降低，卵巢组织形态改善（均p<0.05）。重要的是,上调p-AKT,观察到p-ERK1/2和BCL2的表达，而BAX的表达被抑制（所有p<0.05），提示抑制卵巢细胞凋亡。
结论：我们的研究强调了HUCMSC移植对西藏小型猪模型中CTX诱导的POF的显著治疗效果。
