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离子霉素诱导的小鼠卵母细胞激活可通过增加活性氧反应和 DNA 损伤来破坏胚胎着床前的胚胎发育。

Ionomycin-induced mouse oocyte activation can disrupt preimplantation embryo development through increased reactive oxygen species reaction and DNA damage.

机构信息

Department of Assisted Reproduction, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.

Department of Gynaecology, Guangdong Second Provincial General Hospital, Guangzhou, People's Republic of China.

出版信息

Mol Hum Reprod. 2020 Oct 1;26(10):773-783. doi: 10.1093/molehr/gaaa056.

Abstract

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.

摘要

卵母细胞激活诱导的钙振荡是正常受精和随后胚胎发生的重要过程。在临床辅助生殖中,人工卵母细胞激活(AOA)是提高 ICSI 后受精率为零或低的患者临床结局的有效方法。然而,对于 ICSI 正常受精的情况下,AOA 对胚胎植入前发育的影响知之甚少。在这里,我们使用不同浓度的离子霉素在 ICSI 后激活卵母细胞,并评估能量代谢和胚胎植入前的发育。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,影响了线粒体能量代谢的平衡,导致活性氧(ROS)增加和 ATP 减少。最终,导致 DNA 损伤增加和囊胚形成减少。此外,在培养基中添加维生素 C 可改善 ROS 和 DNA 损伤的增加,并挽救因离子霉素过度激活而导致的异常胚胎发育。这项研究提供了一个视角,即 AOA 的不当应用可能对胚胎植入前的发育产生不利影响。因此,临床 AOA 治疗应谨慎应用。

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