Repair effect of bone marrow mesenchymal stem cells over-expressing miR-21 on chemotherapeutic premature ovarian failure / 解放军医学杂志

ABSTRACT

[Abstract] Objective To explore the repair effects of bone marrow mesenchymal stem cells (BMSCs) over-expressing miR-21 on chemotherapeutic premature ovarian failure (POF) in rats. Methods The expression vector of lentivirus-mediated miR-21 (LV-miR-21) was constructed, and BMSCs were transfected with LV-miR-21 to construct miR-21-BMSCs. A hundred rats were divided into 5 groups (20 each) normal group, model group, miR-21 group, BMSCs group and miR-21-BMSCs group. The chemotherapeutic POF model was established by intraperitoneal injection of cyclophosphamide (CTX) in rats of the latter 4 groups. Then LV-miR-21, BMSCs and miR-21-BMSCs were injected respectively into the bilateral ovaries of the rats in the latter 3 groups, and physiological saline was injected into the rats of normal group and model group. At 15, 30, 45 and 60 days after injection, the estrus cycle, estradiol (E2) and follicle stimulating hormone (FSH) level, ovarian weight, follicle count at all levels, and apoptotic rate of granulosa cells in each group were detected. Results After injection of CTX, the estrus cycle of rats remained regular in normal group, and fell into disorder in the other four groups, of which the number of rats with recovered estrus cycle in the miR-21-BMSCs group was more than the other three groups; The ovarian weight and follicle count at all levels were significantly higher in miR-21-BMSCs group than in model group, miR-21 group and BMSCs group 30, 45 and 60 days after CTX injection (P<0.05); The basal levels of E2 and FSH showed no significant difference in each group during the experiment, while the E2 concentration decreased and FSH concentration increased in all the groups except the normal group. The hormone levels of E2 and FSH in miR-21-BMSCs group (F30d=43.10 and F30d=14.71) were significantly different when compared to those in miR-21 group and BMSCs group (F45d=43.57 and F45d=13.16, P<0.05; and F60d=44.98 and F60d=15.20, P<0.05); The apoptotic rate of ovarian granular cells in miR-21-BMSCs group was significantly lower (F60d=21.20) than that in model group, miR-21 group and BMSCs group (F15d=27.20, F30d=23.60 and F45d=21.80, P<0.05). Conclusion miR-21 may enhance the therapeutic effect of BMMSCs on chemotherapeutic premature ovarian failure, and significantly improve the ovarian structure and function.