Beneficial effects of human umbilical cord mesenchymal stem cell (HUCMSC) transplantation on cyclophosphamide (CTX)-induced premature ovarian failure (POF) in Tibetan miniature pigs

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. 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. 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. Our study highlights the significant therapeutic effects of HUCMSC transplantation on CTX-induced POF in a Tibetan miniature pig model. • The transplantation of HUCMSCs has significant therapeutic effects on CTX-induced POF Tibetan miniature pigs. • HUCMSCs can significantly increase body weight, ovarian index, and E2 levels, and decrease FSH levels in pigs with POF. • HUCMSCs can improve the pathological state of ovarian tissue and increase the number of normal follicles in pigs with POF. • HUCMSCs can significantly inhibit the apoptosis rate of ovarian cells in pigs with POF. • HUCMSCs can significantly increase the expression of p-AKT, p-ERK1/2, and BCL2, and reduce the expression of BAX.