BACKGROUND IVF for the treatment of infertility offers unique opportunities to observe human preimplantation development. Progress in time-lapse technology (TLT) and preimplantation genetic testing (PGT) has greatly expanded our knowledge of developmental patterns leading to a healthy pregnancy or developmental failure. These technologies have also revealed unsuspected plastic properties of the preimplantation embryo, at macromolecular, cellular and multicellular levels. OBJECTIVE AND RATIONALE This review focuses on the emerging concept of plasticity of the human embryo as revealed by recent evidence derived from TLT and PGT, calling for an updated and more precise redefinition of the boundaries between normal and abnormal development. SEARCH METHODS PubMed was used to search the MEDLINE database for peer-reviewed English-language original articles and reviews concerning human preimplantation development. Cross-searches were performed by adopting ‘fertilisation‘, ‘pronucleus’, ‘cleavage’, ‘multinucleation’, ‘compaction’, ‘embryo’, ‘preimplantation genetic testing’, ‘aneuploidy’, mosaicism’, ‘micromanipulation’, ‘time-lapse microscopy’ and ‘IVF/assisted reproduction’ as main terms. The most relevant publications, i.e. those concerning major phenomena occurring during normal and abnormal development—with a focus on the human species—were assessed and discussed critically. OUTCOMES Advances in TLT and PGT have revealed an astonishing plasticity and self-correction ability of the human preimplantation embryo in vitro. At fertilisation, an abnormal number of pronuclei do not always result in the formation of an aneuploid blastocyst. Animal studies and preliminary human observations indicate that combining of parental genomes may occur at the early cleavage stage, if not at fertilisation. Multinucleation occurs with much higher prevalence than previously thought and may be corrected at later cleavage stages. Irregular cleavage (multichotomous, direct, rapid and reverse cleavages) can generate chromosome segregation abnormalities that often lead to developmental arrest, but that sporadically may be confined to cells excluded from the blastocyst, and may sometimes result in viable pregnancy. Mitotic errors can generate mosaic blastocysts, but alternatively normal embryos may form from selective death or clonal depletion of aneuploid cells. WIDER IMPLICATIONS Deviations from developmental dogmas and the increasing evidence of plasticity of the human embryo challenge current embryological notions and suggest the need to write new rules governing cell cycle, cell determination and chromosome segregation during preimplantation development.

中文翻译：

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人类植入前胚胎的可塑性：发育教条、主题变化和自我纠正

背景技术用于治疗不孕症的IVF为观察人类植入前发育提供了独特的机会。延时技术 (TLT) 和植入前基因检测 (PGT) 的进步极大地扩展了我们对导致健康怀孕或发育失败的发育模式的了解。这些技术还揭示了植入前胚胎在大分子、细胞和多细胞水平上意想不到的可塑性。目标和理由 本综述重点关注人类胚胎可塑性这一新兴概念，正如最近从 TLT 和 PGT 得出的证据所揭示的那样，要求对正常发育和异常发育之间的界限进行更新和更精确的重新定义。搜索方法 PubMed 用于在 MEDLINE 数据库中搜索经过同行评议的英语原创文章和有关人类植入前发育的评论。通过采用“受精”、“原核”、“卵裂”、“多核”、“压实”、“胚胎”、“植入前基因检测”、“非整倍体”、嵌合体、“显微操作”、“时间”进行交叉搜索-失效显微镜”和“IVF/辅助生殖”作为主要术语。最相关的出版物，即关于正常和异常发育过程中发生的主要现象的出版物——重点关注人类物种——进行了批判性评估和讨论。结果 TLT 和 PGT 的进展揭示了人类植入前胚胎在体外具有惊人的可塑性和自我校正能力。受精时，异常数量的原核并不总是导致形成非整倍体囊胚。动物研究和人类初步观察表明，亲本基因组的结合可能发生在早期卵裂阶段，如果不是在受精阶段。多核的发生率比以前认为的要高得多，并且可以在后期的分裂阶段得到纠正。不规则的卵裂（多分裂、直接、快速和反向卵裂）可产生染色体分离异常，这通常会导致发育停滞，但偶尔可能仅限于被排除在胚泡之外的细胞，有时可能导致可存活的妊娠。有丝分裂错误可产生马赛克囊胚，但正常胚胎可能由选择性死亡或非整倍体细胞的克隆耗竭形成。