Human Umbilical Cord Mesenchymal Stem Cells Enhance Folliculogenesis and Fertility in Premature Ovarian Failure Mice via Regulating Steroid synthesis

Abstract

Abstract Background Premature Ovarian Failure (POF) is a dysfunction that severely impacts women's physiological health and reproductive function. Human umbilical cord mesenchymal stem cell (hUCMSC) transplantation offers a promising therapeutic option for restoring ovarian function. However, its efficacy and underlying mechanisms are not yet fully understood. Methods A POF mouse model was established using cyclophosphamide induction, and hUCMSCs were transplanted into the ovaries through in situ injection. Treatment efficacy was evaluated by assessing hormone levels, estrous cycle, follicle count, and reproductive outcomes. Furthermore, metabolomic sequencing was performed on the ovarian tissues of mice to explore the mechanism underlying the therapeutic effect of hUCMSCs. Results Compared to the POF control group, the hUCMSC treatment group showed significant improvements: primordial and primary follicle counts increased by 8-fold and 5-fold respectively, while atretic follicle ratios decreased by 50%. Pregnancy rates in treatment group increased from 25% to 75%, with average litter sizes rising from 1.5 pups/litter to 4.5 pups/litter. The expression of key genes (Cyp11a1, Cyp19a1, Star) in the steroidogenesis pathway was significantly upregulated in ovarian tissues, which restored the levels of steroid hormones such as progesterone and thereby stabilized serum sex hormone levels. Conclusions In situ injection of hUCMSCs can restore ovarian function and fertility in POF mice by reducing granulosa cell apoptosis and upregulating steroidogenesis pathways.