Protective Effects of Puerarin on Premature Ovarian Failure via Regulation of Wnt/β-catenin Signaling Pathway and Oxidative Stress

This study was designed to investigate the protective effects of puerarin (PUE), which work via the Wnt/β-catenin signaling pathway, and oxidative stress in the premature ovarian failure (POF) model. Two-month-old female mice were randomly divided into four groups. One group was used as the control, and the other three groups were injected with cyclophosphamide and busulfan to create POF models. Two POF treatment groups were gavaged with 100 or 200 mg/kg PUE for 28 days. Next, the ovaries were fixed, and the numbers of different stage follicles were measured, and the ovarian surface epithelium (OSE) was collected. Oct4 and Mvh expression, Wnt/β-catenin signaling pathway activity, the oxidative stress factors SOD2 and Nrf2, and the apoptosis-related proteins Bcl-2 and Bax were detected by IHC, RT-QPCR, and western blotting. We found that the number of follicles, Oct4 and Mvh expression, and Wnt/β-catenin-signaling activity were reduced in the POF groups ( p < 0.05 or p < 0.001). After PUE treatment, the follicle number and the primordial follicle ratio increased ( p < 0.01), while the atresia ratio decreased ( p < 0.01). In addition, the expression levels of Oct4, Mvh, Wnt1, β-catenin, cyclin D1, SOD2, and Nrf2 showed obvious recovery compared with levels in the POF group ( p < 0.01, p < 0.05, or p < 0.001). The Bcl-2/Bax ratio in the POF model had reduced by about 60% compared with the control group ( p < 0.001) and improved by about 50% after PUE treatment ( p < 0.001). In conclusion, PUE may improve the survival of female reproductive stem cells (FGSCs) and play a protective role against POF via a mechanism involving the Wnt/β-catenin signaling pathway, as well as relieving oxidative stress. Further investigations should focus on the culture of oocytes and FGSCs in vitro in a PUE environment with inhibitors or agonists of the Wnt signaling pathway.