Abstract:

Objective To observe the effects of different concentrations of cyclophosphamide (CTX) induced premature ovarian insufficiency (POI) model in mice and investigate the mechanism of injury. Method 75 mg/kg CTX, 120 mg/kg CTX and 120 mg/kg CTX +12 mg/kg Busulfan were used to induce POI model in C57BL/6J female mice according to the study. Ovarian index, estradiol (E₂) and follicle stimulating hormone (FSH) were determined. The expression level and pattern of SIRT5 and FOXO3a protein were investigated by western blots. Result Compared with control group, all concentration of CTX (75 mg/kg, 120 mg/kg, 120 mg/kg CTX+12 mg/kg Busulfan) could induced POI injury. However, the mild change in ovarian index and E₂ compared to other two group after 120 mg/kg CTX induced, while rough coat, reduced gloss, unresponsive and in worst condition was showed in the treatment of 120 mg/kg CTX+12 mg/kg Busulfan. Western blot results showed that FOXO3a expression was significantly down-regulated and SIRT5 expression did not significantly change after 75 mg/kg CTX modeling, whereas both SIRT5 and FOXO3a expression were significantly down-regulated after 120 mg/kg CTX modeling; on days 2 and 7 after 120 mg/kg CTX modeling, SIRT5 and FOXO3a expression were significantly down-regulated in the ovarian tissue on day 2 and day 7 after 120 mg/kg CTX modeling, and the greatest change in expression level was observed on day 7. Conclusion 120 mg/kg CTX is the optimal concentration for inducing POI in mice, and the SIRT5-FOXO3a pathway may be the mechanism of its injury action.

Key words: Cyclophosphamide, Premature ovarian insufficiency, Mice model, SIRT5-FOXO3a pathway, Mechanism