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活性氧信号在体外培养的哺乳动物卵母细胞质量下降中的作用:抗氧化剂的保护作用。

Reactive oxygen species signalling in the deterioration of quality of mammalian oocytes cultured in vitro: Protective effect of antioxidants.

作者信息

Pandey Ashutosh N, Yadav Pramod K, Premkumar Karuppanan V, Tiwari Meenakshi, Pandey Ajai K, Chaube Shail K

机构信息

Cell Physiology Laboratory, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi 221005, India.

Department of Kayachikitsa, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India.

出版信息

Cell Signal. 2024 May;117:111103. doi: 10.1016/j.cellsig.2024.111103. Epub 2024 Feb 15.

Abstract

The in vitro fertilization (IVF) is the first choice of infertile couples worldwide to plan for conception. Besides having a significant advancement in IVF procedure, the success rate is still poor. Although several approaches have been tested to improve IVF protocol, minor changes in culture conditions, physical factors and/or drug treatment generate reactive oxygen species (ROS) in oocytes. Due to large size and huge number of mitochondria, oocyte is more susceptible towards ROS-mediated signalling under in vitro culture conditions. Elevation of ROS levels destabilize maturation promoting factor (MPF) that results in meiotic exit from diplotene as well as metaphase-II (M-II) arrest in vitro. Once meiotic exit occurs, these oocytes get further arrested at metaphase-I (M-I) stage or metaphase-III (M-III)-like stage under in vitro culture conditions. The M-I as well as M-III arrested oocytes are not fit for fertilization and limits IVF outcome. Further, the generation of excess levels of ROS cause oxidative stress (OS) that initiate downstream signalling to initiate various death pathways such as apoptosis, autophagy, necroptosis and deteriorates oocyte quality under in vitro culture conditions. The increase of cellular enzymatic antioxidants and/or supplementation of exogenous antioxidants in culture medium protect ROS-induced deterioration of oocyte quality in vitro. Although a growing body of evidence suggests the ROS and OS-mediated deterioration of oocyte quality in vitro, their downstream signalling and related mechanisms remain poorly understood. Hence, this review article summarizes the existing evidences concerning ROS and OS-mediated downstream signalling during deterioration of oocyte quality in vitro. The use of various antioxidants against ROS and OS-mediated impairment of oocyte quality in vitro has also been explored in order to increase the success rate of IVF during assisted reproductive health management.

摘要

体外受精(IVF)是全球不孕夫妇计划受孕的首选方法。尽管IVF程序有了显著进展,但成功率仍然很低。虽然已经测试了几种方法来改进IVF方案,但培养条件、物理因素和/或药物治疗的微小变化会在卵母细胞中产生活性氧(ROS)。由于卵母细胞体积大且线粒体数量众多,在体外培养条件下,卵母细胞更容易受到ROS介导的信号传导的影响。ROS水平的升高会使成熟促进因子(MPF)不稳定,导致减数分裂从双线期退出,并在体外导致中期-II(M-II)停滞。一旦发生减数分裂退出,这些卵母细胞在体外培养条件下会进一步停滞在中期-I(M-I)阶段或类似中期-III(M-III)的阶段。停滞在M-I和M-III阶段的卵母细胞不适合受精,限制了IVF的结果。此外,过量ROS的产生会导致氧化应激(OS),引发下游信号传导,启动各种死亡途径,如凋亡、自噬、坏死性凋亡,并在体外培养条件下使卵母细胞质量恶化。在培养基中增加细胞内酶抗氧化剂和/或补充外源性抗氧化剂可保护卵母细胞质量免受ROS诱导的体外恶化。尽管越来越多的证据表明ROS和OS介导的卵母细胞质量在体外的恶化,但其下游信号传导和相关机制仍知之甚少。因此,这篇综述文章总结了关于ROS和OS介导的卵母细胞质量在体外恶化过程中下游信号传导的现有证据。为了提高辅助生殖健康管理期间IVF的成功率,还探索了使用各种抗氧化剂来对抗ROS和OS介导的卵母细胞质量损伤。

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