Continuous treatment with cisplatin induces the oocyte death of primordial follicles without activation.
Continuous treatment with cisplatin induces the oocyte death of primordial follicles without activation.
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DOI：
10.1096/fj.202001461rr
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发表时间：
2020-10
期刊：
影响因子：
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通讯作者：
Kim SY
中科院分区：
文献类型：
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作者：
Eldani M;Luan Y;Xu PC;Bargar T;Kim SY
化疗直接或间接地短期或持续地影响器官。内分泌器官对癌症治疗特别敏感，导致患者担心他们的生活质量。对卵巢的副作用包括损害卵巢储备，导致卵泡丧失、内分泌激素缺乏和不孕。先前有研究表明，连续使用2mg /kg顺铂治疗15天可以激活原始卵泡，这表明原始卵泡卵母细胞的反应取决于顺铂浓度和给药频率。然而，我们的研究结果表明，连续使用2 mg/kg顺铂治疗15天与连续使用5 mg/kg顺铂治疗15天的结果相同：原始卵泡中的卵母细胞死亡，无活化迹象。此外，联合注射褪黑素和顺铂的动物与接受顺铂治疗的动物没有任何显著差异，这与已知的结果相反。褪黑素的代谢物6-羟基褪黑素不能防止卵泡破坏，这意味着褪黑素不能直接或间接地保护卵巢卵泡。总之，我们的数据支持抗顺铂的卵细胞保护剂必须靶向控制原始卵泡卵母细胞死亡途径的分子。
Chemotherapy directly or indirectly affects organs in a short-term or continuous manner. Endocrine organs are especially sensitive to cancer treatment, leading to concerns among patients regarding their quality of life afterward. Side-effects to the ovary include damage to the ovarian reserve, resulting in follicle loss, endocrine hormone deficiency, and infertility. It has been previously demonstrated that continuous treatment with 2 mg/kg cisplatin for 15 days can activate primordial follicles, suggesting that the response in the oocytes of primordial follicles was dependent on cisplatin concentration and administration frequency. However, our results demonstrate that continuous treatment with 2 mg/kg cisplatin for 15 days leads to the same consequence as with the continuous treatment of 5 mg/kg cisplatin: the death of oocytes in primordial follicles without indication of activation. Moreover, animals co-injected with melatonin and cisplatin did not display any significant differences from those treated with cisplatin only contrary to the known results. 6-hydroxymelatonin, a metabolite of melatonin, could not prevent follicle destruction, implying that melatonin does not confer the protection of ovarian follicles, either directly or indirectly. Altogether, our data support that fertoprotectants against cisplatin must target molecules that control cell death pathways in the oocytes of primordial follicles.