title: Protective effect of a gonadotropin-releasing hormone analogue on chemotherapeutic agent-induced ovarian gonadotoxicity: a mouse model.
abstract: OBJECTIVE
  To demonstrate the protective effect of triptorelin, a GnRH analogue, on chemotherapy-induced ovarian gonadotoxicity.
  
  
  METHODS
  Twenty-four sexually mature, virgin, female FVB/NJNarl mice were divided into four groups: busulfan (B); low-dose triptorelin plus busulfan (T(L)+B); high-dose triptorelin plus busulfan (T(H)+B); and control. Mice in the T(L)+B and T(H)+B groups were injected with 3.8 and 38 mg/kg of triptorelin subcutaneously, respectively. Four weeks later, mice in the B, T(L)+B, and T(H)+B groups were injected with busulfan intraperitoneally at a dose of 36 mg/kg. Histologic examinations were performed 4 weeks later.
  
  
  RESULTS
  Obvious destruction of ovarian structure and significant depletion of primordial, primary, and secondary follicles were demonstrated in the B group compared with the control group, affirming the gonadotoxicity of busulfan. In the T(L)+B group, a greater number of larger primordial and primary follicles were enumerated compared with the B group; however, statistical significance was not achieved. In the T(H)+B group, the number of primordial and primary follicles was significantly greater than in the B group, and the ovarian tissue in the T(H)+B group was spared, demonstrating the effect of triptorelin pre-treatment on ovarian protection.
  
  
  CONCLUSIONS
  Our results have demonstrated a dose-dependent protective effect against gonadotoxic chemotherapy of a GnRH analogue on ovarian reserve, thus suggesting a novel application of GnRH analogues in fertility preservation.
authors.affiliation: Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Shun-Jen
authors.initials: SJ
authors.lastname: Tan
authors.forename: Yu-Chi
authors.initials: YC
authors.lastname: Yeh
authors.forename: Wei-Jen
authors.initials: WJ
authors.lastname: Shang
authors.forename: Gwo-Jang
authors.initials: GJ
authors.lastname: Wu
authors.forename: Jah-Yao
authors.initials: JY
authors.lastname: Liu
authors.forename: Chi-Huang
authors.initials: CH
authors.lastname: Chen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002066:Busulfan / Q000009:adverse effects*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives; D051379:Mice; D006080:Ovarian Follicle / Q000187:drug effects; D010053:Ovary / Q000187:drug effects; D016649:Primary Ovarian Insufficiency / Q000517:prevention & control*; D017329:Triptorelin Pamoate / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D017329:Triptorelin Pamoate; D007987:Gonadotropin-Releasing Hormone; D002066:Busulfan