Abstract:
Vinorelbine is a commonly used drug to treat various malignancies, such as breast cancer, non-small cell lung cancer, and metastatic pleural mesothelioma. Its side effects include severe neutropenia, local phlebitis, gastrointestinal reactions, and neurotoxicity. In view of the scarcity of research on vinorelbine\'s reproductive toxicity, this study evaluated the impact of vinorelbine ditartrate, a commonly used form of vinorelbine, on oocyte maturation in vitro. Our investigation revealed that vinorelbine ditartrate had no effect on oocyte meiotic resumption. However, it did reduce the rate of first polar body extrusion, suggesting that it could significantly impede the meiotic maturation of oocytes. Vinorelbine ditartrate exposure was found to disturb the regular spindle assembly and chromosome alignment, leading to the continuous activation of the spindle assembly checkpoint (SAC) and a delayed activation of the anaphase-promoting complex/cyclosome (APC/C), ultimately causing aneuploidy in oocytes. Consequently, the administration of vinorelbine is likely to result in oocyte aneuploidy, which can be helpful in providing a drug reference and fertility guidance in a clinical context.
摘要:
长春瑞滨是治疗各种恶性肿瘤的常用药物,比如乳腺癌,非小细胞肺癌,和转移性胸膜间皮瘤。它的副作用包括严重的中性粒细胞减少,局部静脉炎,胃肠道反应,和神经毒性。鉴于长春瑞滨生殖毒性研究的不足,这项研究评估了长春瑞滨双酒石酸盐的影响,长春瑞滨的一种常用形式,卵母细胞体外成熟。我们的研究表明,长春瑞滨对卵母细胞减数分裂的恢复没有影响。然而,它确实降低了第一极体挤出的速度,这表明它可以显著阻碍卵母细胞的减数分裂成熟。发现二酒石酸长春瑞滨暴露会干扰常规的纺锤体组装和染色体排列,导致主轴组装检查点(SAC)的持续激活和后期促进复合物/环(APC/C)的延迟激活,最终导致卵母细胞的非整倍性。因此,长春瑞滨的给药可能导致卵母细胞非整倍体,这有助于在临床背景下提供药物参考和生育指导。