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DNA甲基化、环境暴露与早期胚胎发育

DNA methylation, environmental exposures and early embryo development.

作者信息

Breton-Larrivée Mélanie, Elder Elizabeth, McGraw Serge

机构信息

Department of Biochemistry and Molecular Medicine, Université de Montréal, Research Center of the CHU Sainte-Justine. Montreal, Canada.

Department of Obstetrics & Gynecology, Université de Montréal, Research Center of the CHU Sainte-Justine, Montréal, Canada.

出版信息

Anim Reprod. 2019 Oct 23;16(3):465-474. doi: 10.21451/1984-3143-AR2019-0062.

Abstract

The first crucial step in the developmental program occurs during pre-implantation, the time after the oocyte has been fertilized and before the embryo implants in the uterus. This period represents a vulnerable window as the epigenome undergoes dynamic changes in DNA methylation profiles. Alterations in the early embryonic reprogramming wave can impair DNA methylation patterns and induce permanent changes to the developmental program, leading to the onset of adverse health outcomes in offspring. Although there is an increasing body of evidence indicating that harmful exposures during pre-implantation embryo development can trigger lasting epigenetic alterations in offspring, the mechanisms are still not fully understood. Since physiological or pathological changes in DNA methylation can occur as a response to environmental cues, proper environmental milieu plays a critical role in the success of embryonic development. In this review, we depict the mechanisms behind the embryonic epigenetic reprogramming of DNA methylation and highlight how maternal environmental stressors (e.g., alcohol, heat stress, nutrient availability) during pre-implantation and assisted reproductive technology procedures affect development and DNA methylation marks.

摘要

发育程序的第一个关键步骤发生在植入前阶段,即卵母细胞受精后、胚胎植入子宫前的这段时间。这一时期是一个脆弱的窗口期,因为表观基因组的DNA甲基化图谱会发生动态变化。早期胚胎重编程浪潮中的改变会损害DNA甲基化模式,并导致发育程序的永久性变化,从而导致后代出现不良健康后果。尽管越来越多的证据表明,植入前胚胎发育期间的有害暴露会引发后代持久的表观遗传改变,但其机制仍未完全了解。由于DNA甲基化的生理或病理变化可能是对环境线索的反应,适当的环境环境对胚胎发育的成功起着关键作用。在这篇综述中,我们描述了DNA甲基化胚胎表观遗传重编程背后的机制,并强调了植入前和辅助生殖技术过程中母体环境应激源(如酒精、热应激、营养可利用性)如何影响发育和DNA甲基化标记。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41f8/7234019/6db3f5d2579d/1984-3143-ar-16-3-465-gf01.jpg

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