Human umbilical cord mesenchymal stromal cells ameliorate ovarian damage and restore function in Premature Ovarian Insufficiency rat model

Premature ovarian insufficiency (POI) is a debilitating condition characterized by infertility and systemic health decline, with limited effective therapeutic options. This study explores the therapeutic potential of human umbilical cord-derived mesenchymal stromal cells (hUC-MSCs) in a cyclophosphamide (CTX)-induced rat model of POI. The POI rats were administered low or high doses of hUC-MSCs via tail vein transplantation. Ovarian function was evaluated through monitoring of the estrous cycle, serum hormone analysis, ovarian histomorphology, follicle counting, and mating assays. Immunohistochemistry was employed to assess the expression of proteins related to apoptosis and angiogenesis. Additionally, in vitro co-culture assays were conducted to evaluate the immunomodulatory capacity of hUC-MSCs. The results indicated that hUC-MSC transplantation restored estrous cyclicity, normalized hormone levels, increased follicle counts, and improved pregnancy outcomes in a dose-dependent manner. Histological analysis indicated a reduction in atretic follicles and an enhancement of ovarian structure. Mechanistically, hUC-MSCs were found to attenuate apoptosis by modulating the expression of Bcl-2 and Caspase-3 and to promote angiogenesis through the upregulation of VEGF. In vitro, hUC-MSCs demonstrated significant immunomodulatory effects, including the suppression of pro-inflammatory cytokine secretion and the promotion of regulatory T cell expression. In conclusion, hUC-MSCs effectively ameliorate CTX-induced ovarian damage, highlighting their promise as a regenerative therapy for POI.