GNRH Agonists and Antagonists in Rescue for Cyclophosphamide-Induced Ovarian Damage: Friend or Foe?

Abstract

To find out if GnRH agonist (GnRHa) and GnRH antagonist (GnRHant) offer ovarian protection from cyclophosphamide (Cyc) and if AMH expression is affected.

This experimental study was conducted in Baskent University Animal research laboratory and 66 virgin Wistar albino rats were assigned to six groups. The control group received intraperitoneal saline injection. The GnRHa group had a single dose of leuprolide acetate (1 mg/kg) 28 days prior to saline injection. The GnRHant group had a single dose of cetrorelix acetate (0.1 mg/kg) 1 h prior to saline injection. The Cyc group had a single intraperitoneal dose of Cyc (75 mg/kg). The GnRHa+Cyc group had a single dose of leuprolide acetate (1 mg/kg) 28 days prior to Cyc (75 mg/kg). The GnRHant+Cyc group had single dose of cetrorelix acetate (0.1 mg/kg) 1 h prior to Cyc (75 mg/kg). At day 35, the animals were euthanized, and their ovaries were removed. Primordial follicles were counted and AMH expression was determined. The Kruskal-Wallis, chi (2), or Fisher's exact test was used where appropriate. p < 0.05 was considered statistically significant.

PMF count was reduced in GnRHant (p < 0.01) and Cyc (p < 0.01) groups. Cyc, GnRHa+Cyc and GnRHant+Cyc groups had similar numbers of PMF. AMH expression was reduced in Cyc, GnRHa+Cyc and GnRHant+Cyc groups (p < 0.01).

Neither GnRHa nor GnRHant can offer protection against Cyc-induced damage. GnRHant itself reduces the number of primordial follicles.