The Effects of Inhibin B in the Chemotherapy Drug-Induced Premature Ovarian Insufficiency Mice and hPMSCs Treatment.

Abstract

Human placenta mesenchymal stem cells (hPMSCs), have been extensively investigated on the treatment of many diseases. This study was to explore the effects of hPMSCs treatment on the chemotherapy drug-induced premature ovarian insufficiency (POI) mice. Cyclophosphamide (120mg/kg) and busulfan (30mg/kg) or cyclophosphamide (70mg/kg) induced POI mice were used and hPMSCs were injected through tail vein. The hormone levels of serum, morphological changes, the expression and quantitative analysis of inhibin B (INHBB) and FSHR protein, and apoptosis of granulosa cells in ovary were detected. The granulosa cells (GCs) were detected from ovaries of mice and the different concentration of cyclophosphamide on GCs were detected by MTT assay. The apoptosis of GCs was detected by FITC Annexin V Apoptosis Detection Kit. The significant increase in FSH and decrease in E2 and INHBB were observed. Expression of human nuclei was observed in the stroma of ovaries. INHBB and FSHR levels of ovaries were reduced in the POI mice. Following hPMSCs treatment, the amounts of INHBB and FSHR significantly increased close to normal levels. The granulosa cells apoptosis increased in the POI ovaries but decreased after hPMSCs treatment. Moreover, cyclophosphamide has no effect on the GCs and no statistic difference was measured in vitro. The effects of hPMSCs treatment reduce the apoptosis of granulosa cells and restore the ovarian reserve capacity in chemotherapeutic drug-induced POI mice. The data help to further explore new potential clinical therapeutic approach for POI patients.