Melatonin Prevents Postovulatory Oocyte Aging in the Mouse and Extends the Window for Optimal Fertilization In Vitro
Melatonin Prevents Postovulatory Oocyte Aging in the Mouse and Extends the Window for Optimal Fertilization In Vitro
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DOI：
10.1095/biolreprod.112.106450
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发表时间：
2013-03-01
影响因子：
3.6
通讯作者：
Aitken, R. John
中科院分区：
文献类型：
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作者：
Lord, Tessa;Nixon, Brett;Aitken, R. John
中期II卵母细胞的质量在排卵后迅速恶化，这是由于与受精能力受损、发育能力中断和胚胎吸收可能性增加相关的衰老过程的结果。由于氧化应激加速卵母细胞的凋亡并影响其受精能力，本研究旨在探讨氧化应激在小鼠卵母细胞体外排卵后老化过程中的意义。我们研究了强大的抗氧化剂褪黑素在补充卵母细胞培养液时延缓衰老过程的能力。本研究表明，卵母细胞在培养8h后即可发生氧化应激，并与早期凋亡标志物如磷脂酰丝氨酸外化的出现相吻合，16h后出现caspase激活(P<；0.05)和卵母细胞衰老的形态证据。重要的是，在卵母细胞培养液中添加1 mM褪黑素能够显著减轻卵母细胞氧化应激的时间依赖性(P<；0.05)，从而显著延迟卵母细胞凋亡的发生(P<；0.05)。此外，添加褪黑激素延长了8和16h卵母细胞体外受精的最佳时间窗(P<；0.05)，并显著提高了胚胎的质量(P<；0.01)。我们得出结论，褪黑素在临床上可能是一种有用的工具，可以防止长时间体外培养后卵母细胞质量的随时间变化的恶化。
The quality of metaphase II oocytes deteriorates rapidly following ovulation as the result of an aging process associated with impaired fertilizing potential, disrupted developmental competence, and increased likelihood of embryonic resorption. Because oxidative stress accelerates the onset of apoptosis in oocytes and influences their capacity for fertilization, this study aimed to characterize the significance of such stress in the postovulatory aging of mouse oocytes in vitro. We investigated the ability of the potent antioxidant melatonin to arrest the aging process when used to supplement oocyte culture medium. This study demonstrated that oxidative stress may occur in oocytes after as little as 8 h in culture and coincides with the appearance of early apoptotic markers such as phosphatidylserine externalization, followed 16 h later by caspase activation (P < 0.05) and morphological evidence of oocyte senescence. Importantly, supplementation of oocyte culture medium with 1 mM melatonin was able to significantly relieve the time-dependent appearance of oxidative stress in oocytes (P < 0.05) and, as a result, significantly delay the onset of apoptosis (P < 0.05). Furthermore, melatonin supplementation extended the optimal window for fertilization of oocytes aged for 8 and 16 h in vitro (P < 0.05) and significantly improved the quality of the resulting embryos (P < 0.01). We conclude that melatonin may be a useful tool in a clinical setting to prevent the time-dependent deterioration of oocyte quality following prolonged culture in vitro.