BACKGROUND Most tissues in the body rely on the presence of gap junctions in order to couple their component cells electrically and metabolically via intercellular transport of ions, metabolites and signalling agents. As a result, cells within tissues achieve a high degree of, 'metabolic homogeneity' which enables them to develop in an integrated way and co-ordinate their response to physiological signals and environmental cues. Unusually, the developing mammalian preimplantation embryo does not form functional gap junctions until it has divided into 8 or more cells. We discuss the implications of this 'missing link' during the first few days of development for the maintenance of homogeneity between embryonic cells and for the co-ordination of the embryonic response to intrinsic genetic damage and external environmental signals. METHODS No systematic review has been carried out. The physiology of preimplantation development and the general nature of gap junctions have been reviewed briefly before examining experimental evidence which addresses the following points: (i) whether there are functional differences between early blastomeres; (ii) when during preimplantation development the embryo is most sensitive to environmental perturbation and (iii) the consequences for early embryos of ablating gap junction formation and function. RESULTS AND CONCLUSIONS General conclusions are confounded by species differences, especially in the timing of embryonic genome activation (EGA) and the extent of intrinsic genotypic and phenotypic variation (low in embryos from inbred mice; high in human embryos). Nevertheless, we propose that the absence of gap junctions requires cleavage stage mammalian embryos to behave cell autonomously in a metabolic sense, contributes to their heightened sensitivity to environmental perturbation compared with the later stages of preimplantation development and poses more problems in the early human embryo, where there is a high degree of heterogeneity between the blastomeres. We argue that the legacy of metabolic heterogeneity, in part generated by the absence of gap junctions, is 'rescued' by the onset of apoptosis following EGA. In the context of human-assisted conception, since early embryos lacking gap junctions are more sensitive to environmental stress during cleavage, this would support transfer to the natural environment as early as possible after fertilization.

中文翻译：

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植入前发育过程中的代谢异质性：缺失的环节？

背景技术身体中的大多数组织依赖于间隙连接的存在，以便通过离子、代谢物和信号剂的细胞间运输以电和代谢方式耦合它们的组成细胞。结果，组织内的细胞达到了高度的“代谢同质性”，这使它们能够以一种综合的方式发展，并协调它们对生理信号和环境信号的反应。不同寻常的是，发育中的哺乳动物植入前胚胎在分裂成 8 个或更多细胞之前不会形成功能性间隙连接。我们讨论了在发育的最初几天，这种“缺失环节”对维持胚胎细胞之间的同质性以及协调胚胎对内在遗传损伤和外部环境信号的反应的影响。方法 未进行系统评价。在检查涉及以下几点的实验证据之前，已经简要回顾了植入前发育的生理学和间隙连接的一般性质：（i）早期卵裂球之间是否存在功能差异；(ii) 当胚胎在植入前发育过程中对环境扰动最敏感时，以及 (iii) 消融间隙连接形成和功能对早期胚胎的影响。结果和结论 一般结论因物种差异而混淆，特别是在胚胎基因组激活 (EGA) 的时间以及内在基因型和表型变异的程度（近交小鼠胚胎中低；人类胚胎中高）。尽管如此，我们提出，间隙连接的缺失需要分裂阶段的哺乳动物胚胎在代谢意义上自主地表现细胞，与植入前发育的后期相比，它们对环境扰动的敏感性更高，并且在早期人类胚胎中造成了更多问题，其中有是卵裂球之间的高度异质性。我们认为，代谢异质性的遗产，部分是由于缺乏间隙连接而产生的，被 EGA 后细胞凋亡的开始“拯救”。在人工受孕的背景下，由于缺乏间隙连接的早期胚胎在卵裂过程中对环境压力更敏感，这将有助于在受精后尽早转移到自然环境中。