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氧化应激与DNA甲基化改变:生殖领域的同一枚硬币的两面。

Oxidative stress and alterations in DNA methylation: two sides of the same coin in reproduction.

作者信息

Menezo Yves J R, Silvestris Erica, Dale Brian, Elder Kay

机构信息

London Fertility Associates, Harley St, London, UK; Laboratoire Clement, Avenue d'Eylau, Paris, France.

Clinique Natecia, Lyon, France.

出版信息

Reprod Biomed Online. 2016 Dec;33(6):668-683. doi: 10.1016/j.rbmo.2016.09.006. Epub 2016 Sep 27.

Abstract

The negative effect of oxidative stress on the human reproductive process is no longer a matter for debate. Oxidative stress affects female and male gametes and the developmental capacity of embryos. Its effect can continue through late stages of pregnancy. Metabolic disorders and psychiatric problems can also be caued by DNA methylation and epigenetic errors. Age has a negative effect on oxidative stress and DNA methylation, and recent observations suggest that older men are at risk of transmitting epigenetic disorders to their offspring. Environmental endocrine disruptors can also increase oxidative stress and methylation errors. Oxidative stress and DNA methylation feature a common denominator: the one carbon cycle. This important metabolic pathway stimulates glutathione synthesis and recycles homocysteine, a molecule that interferes with the process of methylation. Glutathione plays a pivotal role during oocyte activation, protecting against reactive oxygen species. Assisted reproductive techniques may exacerbate defects in methylation and epigenesis. Antioxidant supplements are proposed to reduce the risk of potentially harmful effects, but their use has failed to prevent problems and may sometimes be detrimental. New concepts reveal a significant correlation between oxidative stress, methylation processes and epigenesis, and have led to changes in media composition with positive preliminary clinical consequences.

摘要

氧化应激对人类生殖过程的负面影响已不再是一个有争议的问题。氧化应激会影响雌性和雄性配子以及胚胎的发育能力。其影响可能会持续到妊娠后期。代谢紊乱和精神问题也可能由DNA甲基化和表观遗传错误引起。年龄对氧化应激和DNA甲基化有负面影响,最近的观察表明,老年男性有将表观遗传疾病遗传给后代的风险。环境内分泌干扰物也会增加氧化应激和甲基化错误。氧化应激和DNA甲基化有一个共同的特点:一碳循环。这条重要的代谢途径刺激谷胱甘肽的合成并回收同型半胱氨酸,同型半胱氨酸是一种干扰甲基化过程的分子。谷胱甘肽在卵母细胞激活过程中起关键作用,可抵御活性氧。辅助生殖技术可能会加剧甲基化和表观遗传的缺陷。有人提出使用抗氧化补充剂来降低潜在有害影响的风险,但它们的使用未能预防问题,有时可能还会有害。新的概念揭示了氧化应激、甲基化过程和表观遗传之间的显著相关性,并导致了培养基成分的变化,初步临床结果良好。

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