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Modulating oxidative stress and epigenetic homeostasis in preimplantation IVF embryos
Zygote ( IF 1.7 ) Pub Date : 2021-07-27 , DOI: 10.1017/s0967199421000356
Yves Menezo 1 , Patrice Clement 1 , Brian Dale 2 , Kay Elder 3
Affiliation  

Assisted reproductive technology is today considered a safe and reliable medical intervention, with healthy live births a reality for many IVF and ICSI treatment cycles. However, there are increasing numbers of published reports describing epigenetic/imprinting anomalies in children born as a result of these procedures. These anomalies have been attributed to methylation errors in embryo chromatin remodelling during in vitro culture. Here we re-visit three concepts: (1) the so-called ‘in vitro toxicity’ of ‘essential amino acids’ before the maternal to zygotic transition period; (2) the effect of hyperstimulation (controlled ovarian hyperstimulation) on homocysteine in the oocyte environment and the effect on methylation in the absence of essential amino acids; and (3) the fact/postulate that during the early stages of development the embryo undergoes a ‘global’ demethylation. Methylation processes require efficient protection against oxidative stress, which jeopardizes the correct acquisition of methylation marks as well as subsequent methylation maintenance. The universal precursor of methylation [by S-adenosyl methionine (SAM)], methionine, ‘an essential amino acid’, should be present in the culture. Polyamines, regulators of methylation, require SAM and arginine for their syntheses. Cystine, another ‘semi-essential amino acid’, is the precursor of the universal protective antioxidant molecule: glutathione. It protects methylation marks against some undue DNA demethylation processes through ten-eleven translocation (TET), after formation of hydroxymethyl cytosine. Early embryos are unable to convert homocysteine to cysteine as the cystathionine β-synthase pathway is not active. In this way, cysteine is a ‘real essential amino acid’. Most IVF culture medium do not maintain methylation/epigenetic processes, even in mouse assays. Essential amino acids should be present in human IVF medium to maintain adequate epigenetic marking in preimplantation embryos. Furthermore, morphological and morphometric data need to be re-evaluated, taking into account the basic biochemical processes involved in early life.



中文翻译:

调节植入前体外受精胚胎的氧化应激和表观遗传稳态

如今,辅助生殖技术被认为是一种安全可靠的医疗干预措施,在许多 IVF 和 ICSI 治疗周期中,健康的活产已成为现实。然而,越来越多的已发表报告描述了由于这些程序而出生的儿童的表观遗传/印记异常。这些异常归因于体外培养过程中胚胎染色质重塑中的甲基化错误。这里我们重新审视三个概念:(1)所谓的'体外母体向合子过渡期之前“必需氨基酸”的毒性;(2) 过度刺激(受控卵巢过度刺激)对卵母细胞环境中同型半胱氨酸的影响以及在缺乏必需氨基酸的情况下对甲基化的影响;(3)事实/假设在发育的早期阶段胚胎经历了“全球”去甲基化。甲基化过程需要有效防止氧化应激,这会危及甲基化标记的正确获取以及随后的甲基化维持。甲基化的普遍前体 [by S-腺苷蛋氨酸(SAM)],蛋氨酸,“一种必需氨基酸”,应该存在于培养物中。多胺是甲基化的调节剂,其合成需要 SAM 和精氨酸。胱氨酸是另一种“半必需氨基酸”,是通用保护性抗氧化剂分子:谷胱甘肽的前体。在形成羟甲基胞嘧啶后,它通过 10-11 易位 (TET) 保护甲基化标记免受一些不适当的 DNA 去甲基化过程。早期胚胎无法将同型半胱氨酸转化为半胱氨酸,因为胱硫醚 β-合酶途径不活跃。通过这种方式,半胱氨酸是一种“真正的必需氨基酸”。大多数 IVF 培养基不维持甲基化/表观遗传过程,即使在小鼠试验中也是如此。必需氨基酸应存在于人类 IVF 培养基中,以在植入前胚胎中维持足够的表观遗传标记。此外,需要重新评估形态学和形态测量数据,同时考虑到生命早期涉及的基本生化过程。

更新日期:2021-07-27
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