Effect of a gonadotropin-releasing hormone analogue on cyclophosphamide-induced ovarian toxicity in adult mice

Abstract

To evaluate the possible protective effect of low and high dose of triptorelin, a GnRH analogue, on cyclophosphamide-induced ovarian toxicity in adult female mice. Thirty-six sexually mature, virgin, female mice were divided randomly into six groups of six each: control group, low-dose triptorelin (TL) group, high-dose triptorelin (TH) group, cyclophosphamide (CPA) group, low-dose triptorelin plus cyclophosphamide (TL+CPA) group and high-dose triptorelin plus cyclophosphamide (T+CPA) group. Mice in both the TL+CPA and the TH+CPA groups were injected with 3.8 and 38mg/kg of triptorelin subcutaneously, respectively. Fourweeks later, mice in the CPA, TL+CPA and TH+CPA groups were injected with cyclophosphamide, intraperitoneally, at a dose of 50mg/kg. Ovaries were removed 4weeks later and processed for light microscopic examinations. Obvious destruction of ovarian structure and significant depletion of primordial, primary, secondary and antral follicles were demonstrated in the CPA group and compared with the control group, the difference was statistically highly significant (p<0.001), affirming the ovarian toxicity of cyclophosphamide. In the TL+CPA group, there was a significant increase in primordial, primary, secondary and antral follicles compared with the CPA group (p<0.05), showing the effect of triptorelin on ovarian protection. Regarding, the high-dose GnRH agonist the difference was statistically highly significant for primordial and primary follicles (p<0.001). This study has showed a dose-dependent protective effect of GnRH analogue on ovarian reserve against ovarian toxic chemotherapy, thus demonstrating an important role of GnRH analogues in fertility preservation.