Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Axe Immunopathologie, Montréal, Canada.
Faculty of Medicine, Molecular Biology Program, Université de Montréal, Montréal, Canada.
Reproduction. 2023 Feb 14;165(4):R103-R116. doi: 10.1530/REP-22-0144. Print 2023 Apr 1.
Human embryogenesis still remains largely unexplored. This review helps identify some of our current gaps in knowledge pertaining to preimplantation development, which may have implications for understanding fundamental aspects of human development, assisted reproductive technologies, and stem cell biology.
Preimplantation development is arguably one of the most critical stages of embryogenesis. Beginning with the formation of the totipotent zygote post-fertilization, a series of cell divisions, and a complex coordination of physical cues, molecular signals and changes in gene expression lead to the formation of the blastocyst, a structure capable of implanting into the uterine wall. The blastocyst is composed of more specified cellular lineages, which will give rise to every tissue of the developing organism as well as the extra-embryonic lineages which support fetal growth. While the mouse has been used as a model to understand the events of preimplantation development for decades, in recent years, an expanding body of work has been conducted using the human embryo. These studies have identified some crucial species differences, particularly in the transcriptional and spatio-temporal expression of lineage markers and responses to cell signaling perturbations. This review compares recent findings on preimplantation development in mouse and human, with a focus on the specification of the first cellular lineages. Highlighting differences and noting mechanisms that require further examination in the human embryo is of critical importance for both the accurate translation of results from the mouse model and our overall understanding of mammalian development. We further highlight the latest advancement in reproductive research, the development of the 3D stem cell-based models known as 'blastoids'. The knowledge discussed in this review has major clinical implications for assisted reproductive technologies such as in vitro fertilization and for applications in stem cell biology.
胚胎发生的植入前阶段可以说是胚胎发生中最关键的阶段之一。从受精后全能性合子的形成开始,一系列细胞分裂和物理线索、分子信号和基因表达变化的复杂协调导致囊胚的形成,囊胚是一种能够植入子宫壁的结构。囊胚由更特化的细胞谱系组成,这些细胞谱系将产生发育生物体的所有组织以及支持胎儿生长的胚胎外谱系。虽然几十年来,小鼠一直被用作研究植入前胚胎发生事件的模型,但近年来,使用人类胚胎进行的研究工作不断增加。这些研究确定了一些关键的种间差异,特别是在谱系标记的转录和时空表达以及对细胞信号干扰的反应方面。本文比较了小鼠和人类植入前胚胎发生的最新发现,重点是第一个细胞谱系的特化。突出人类胚胎中需要进一步研究的差异和机制对于准确转化小鼠模型的结果以及我们对哺乳动物发育的整体理解至关重要。我们还强调了生殖研究的最新进展,即 3D 基于干细胞的模型“类囊胚”的发展。本文讨论的知识对体外受精等辅助生殖技术以及干细胞生物学的应用具有重要的临床意义。