Preservation of ovarian follicle by concomitant administration of GnRH agonist I, II or GnRH antagonist during Cyclophosphamide or Paclitaxel chemotherapy in mice

Yang, Hoe Saeng

Abstract

OBJECTIVE
The degree of destruction of primordial follicles was investigated following the administration of cyclophosphamide or paclitaxel respectively in mouse ovaies. And then the effect of GnRHa I, GnRH antagonist and GnRHa II on the primordial follicles was evaluated following the administration of cyclophosphamide or paclitaxel.
METHODS
Saline or cyclophosphamide (50 mg/kg or 75 mg/kg) were intraperitoneally injected into seven-week old female ICR mice. GnRHa I (Leuplin(R)), GnRH antagonist (Cetrotide(R)) or GnRHa II (H-6038) was injected into mice, and administered with 50 mg/kg and 75 mg/kg of cyclophosphamide following 9 days treatment with GnRH analogues. After collecting ovaries, H&E staining was performed and the number of primordial follicles was counted. To confirm the induction of apoptosis, TUNEL assay was performed. Another experimental groups of mice were administered with a low concentration (12.5 mg/kg) or a high concentraion (19 mg/kg) of paclitaxel.
RESULTS
Cyclophosphamide and paclitaxel cause mild to moderate destruction of primordial follicles in mouse ovaries. The number of primordial follicles in the group of high dose was noted less than in that of low dose treated with cyclophosphamide or paclitaxel. Increased the apoptotic indices were shown in the group of cyclophosphamide or paclitaxel compared to in saline only treated group. Treatment with GnRHa I, GnRH antagonist and GnRHa II significantly increased the number of primordial follicles at a low concentration of cytotoxic agents (P<0.05), whereas the number of primoridal follicle increased only in GnRHa I antagonist treated group at a high concentration of cyclophosphamide or paclitaxel (P<0.05).
CONCLUSION
The present study shows that GnRH analogues alleviate destruction of primordial follicles caused by cyclophosphamide and paclitaxel in mouse ovaries, suggesting that GnRH analogues may be applicable to increase fertility opportunity in malignant cancer patients of reproductive age planning future pregnancies.