Human umbilical cord mesenchymal stem cells enhance folliculogenesis and fertility in premature ovarian failure mice via regulating steroid synthesis.

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 with 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 30% to 60%, with average litter sizes rising from 1.6 pups/litter to 4.1 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.