Protective effect of a gonadotropin-releasing hormone analogue on chemotherapeutic agent-induced ovarian gonadotoxicity: a mouse model.
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.
Tan
Shun-Jen
SJ
Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
Yeh
Yu-Chi
YC
Shang
Wei-Jen
WJ
Wu
Gwo-Jang
GJ
Liu
Jah-Yao
JY
Chen
Chi-Huang
CH
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*
D000970:Antineoplastic Agents; D017329:Triptorelin Pamoate; D007987:Gonadotropin-Releasing Hormone; D002066:Busulfan