Therapeutic effect of lentivirus-mediated miR-21 on chemotherapy-induced premature ovarian failure in rats / 解放军医学杂志

ABSTRACT

Objective To explore the therapeutic potential of miR-21 in rat model of chemotherapy-induced premature ovarian failure (POF).Methods Lentivirus-mediated miR-21 (LV-miR-21) was constructed successfully in vitro with molecular biology methods.Rats were divided into 4 groups named control group,model group,blank vector group and miR-21 group.Rat models of chem0therapy-induced POF were established in the latter 3 groups by intraperitoneal injection ofcytoxan (CTX).Bilateral ovaries of rats in miR-21 group were injected with LV-miR-21,of rats in blank vector group were injected with lentivirus vector,and rats in model group received no treatment.At 1,15,30,45 and 60 days after the last injection,blood sample was collected,the rats were then sacrificed and the ovaries were removed.The estrous cycle was observed by vaginal smears.The E2 level was detected by chemiluminescent immunoassay,and the follicle stimulating hormone (FSH) level was detected by homologous double antibody radiation immunoassay.Ovary weights were measured,and the follicle count was conducted through observing paraffin section under microscope.The apoptosis of ovarian granulosa cells was analyzed by TUNEL assay.Results During 15-30 days,30-45 days and 45-60 days after the last injection,regular estrous cycle was recovered respectively in 8,5 and 3 rats in miR-21 group.At the 15th,30th,45th and 60th day after the last injection,the E2 level was higher in miR-21 group than in model group and blank vector group,but the FSH level showed the opposite trend (P=0.000).At the 45th and 60th day after the last injection,the follicle numbers at all stages increased markedly in miR-21 group than in model group and blank vector group (P=0.000).At the 30th,45th and 60th day after the last injection,the ovary weights were higher in miR-21 group than in model group and blank vector group.At the 15th,30th,45th and 60th day after the last injection,the apoptosis rate of ovarian granulosa cell were significantly lower in miR-21 group than in model group and blank vector group (P=0.000).Conclusion Up-regulation of miR-21 expression may partly recover the ovarian structure and function damaged by CTX.