Protective effect of a gonadotropin-releasing hormone analogue on chemotherapeutic agent-induced ovarian gonadotoxicity: A mouse model

Protective effect of a gonadotropin-releasing hormone analogue on chemotherapeutic agent-induced ovarian gonadotoxicity: A mouse model
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DOI:
10.1016/j.ejogrb.2009.12.028
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发表时间:
2010-04-01
影响因子:
2.6
通讯作者:
Chen, Chi-Huang
Chen, Chi-Huang
中科院分区:
医学4区
文献类型:
--
作者:
Tan, Shun-Jen;Yeh, Yu-Chi;Chen, Chi-Huang

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目的:探讨促性腺激素类似物雷公干扰素对化疗所致卵巢促性腺激素毒性的保护作用。研究设计:24只性成熟、处女、雌性FVB/NJNarl小鼠分为四组:busulfan (B)组;低剂量triptorelin + busulfan (T-L + B);大剂量雷普妥林加布硫凡(T-H + B);和控制。T-L + B组和T-H + B组小鼠分别皮下注射3.8 mg/kg和38 mg/kg triptorelin。4周后,B组、T-L + B组和T-H + B组小鼠按36 mg/kg的剂量腹腔注射丁硫凡。4周后行组织学检查。结果:与对照组相比,B组卵巢结构明显破坏,原始、初级和次级卵泡明显减少,证实了丹丹的促性腺毒性。与B组相比,T-L + B组有更多的大原始卵泡和原发卵泡;然而,没有达到统计学意义。在T-H + B组中,原始卵泡和原发卵泡数量明显大于B组,并且T-H + B组的卵巢组织得以保留,证明了雷普妥林预处理对卵巢的保护作用。结论:我们的研究结果证明了GnRH类似物对卵巢储备的剂量依赖性保护作用,从而表明GnRH类似物在生育能力保存方面的新应用。爱思唯尔爱尔兰有限公司2009年版权所有版权所有。
Objective: To demonstrate the protective effect of triptorelin, a GnRH analogue, on chemotherapy-induced ovarian gonadotoxicity.Study design: 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.Conclusion: 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. Crown Copyright (C) 2009 Published by Elsevier Ireland Ltd. All rights reserved.