Ionomycin-induced mouse oocyte activation can disrupt preimplantation embryo development through increased reactive oxygen species reaction and DNA damage
Ionomycin-induced mouse oocyte activation can disrupt preimplantation embryo development through increased reactive oxygen species reaction and DNA damage
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离子霉素诱导的小鼠卵母细胞活化可通过增加活性氧反应和 DNA 损伤来破坏植入前胚胎发育
DOI：
10.1093/molehr/gaaa056
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发表时间：
2020-10-01
影响因子：
4
通讯作者：
Lyu, Qifeng
中科院分区：
文献类型：
--
作者：
Chen, Chen;Sun, Tingye;Lyu, Qifeng
钙振荡激活卵母细胞是正常受精和胚胎发育的重要过程。在临床辅助生殖中，人工卵母细胞激活（AOA）是改善ICSI后无效或低受精率患者临床结局的有效方法。然而，在ICSI正常受精的情况下，AOA对植入前胚胎发育的影响知之甚少。在此，我们使用不同浓度的离子霉素激活正常精子ICSI后的卵母细胞，并评估能量代谢和植入前胚胎发育。我们发现高浓度的离子霉素增加了钙振荡模式的频率和幅度，影响线粒体能量代谢的平衡，导致活性氧（ROS）增加和ATP减少。最终，它会增加DNA损伤并减少胚泡形成。此外，向培养基中添加维生素C改善了ROS和DNA损伤的增加，并挽救了由过量离子霉素激活引起的异常胚胎发育。本研究为AOA应用不当可能对植入前胚胎发育产生不良影响提供了一个视角。因此，临床AOA治疗应谨慎管理。
Oocyte activation induced by calcium oscillations is an important process in normal fertilization and subsequent embryogenesis. In the clinical-assisted reproduction, artificial oocyte activation (AOA) is an effective method to improve the clinical outcome of patients with null or low fertilization rate after ICSI. However, little is known about the effect of AOA on preimplantation embryo development in cases with normal fertilization by ICSI. Here, we used ionomycin at different concentrations to activate oocytes after ICSI with normal sperm and evaluated energy metabolism and preimplantation embryo development. We found that a high concentration of ionomycin increased the frequency and amplitude of calcium oscillation patterns, affecting the balance of mitochondrial energy metabolism, leading to increased reactive oxygen species (ROS) and decreased ATP. Eventually, it increases DNA damage and decreases blastocyst formation. In addition, the addition of vitamin C to the culture medium ameliorated the increase in ROS and DNA damage and rescued the abnormal embryo development caused by excessive ionomycin activation. This study provides a perspective that the improper application of AOA may have adverse effects on preimplantation embryo development. Thus, clinical AOA treatment should be cautiously administered.