1Department of Anatomy, Biochemistry and Physiology, Institute for Biogenesis Research, University of Hawaii John A. Burns School of Medicine, Honolulu, Hawaii, USA.
Reproduction. 2022 Aug 22;164(4):R75-R86. doi: 10.1530/REP-21-0478. Print 2022 Oct 1.
Trophectoderm is the first tissue to differentiate in the early mammalian embryo and is essential for hatching, implantation, and placentation. This review article discusses the roles of Ras homolog family members (RHO) and RHO-associated coiled-coil containing protein kinases (ROCK) in the molecular and cellular regulation of trophectoderm formation.
The trophectoderm (TE) is the first tissue to differentiate during the preimplantation development of placental mammals. It constitutes the outer epithelial layer of the blastocyst and is responsible for hatching, uterine attachment, and placentation. Thus, its formation is the key initial step that enables the viviparity of mammals. Here, we first describe the general features of TE formation at the morphological and molecular levels. Prospective TE cells form an epithelial layer enclosing an expanding fluid-filled cavity by establishing the apical-basal cell polarity, intercellular junctions, microlumen, and osmotic gradient. A unique set of genes is expressed in TE that encode the transcription factors essential for the development of trophoblasts of the placenta upon implantation. TE-specific gene expressions are driven by the inhibition of HIPPO signaling, which is dependent on the prior establishment of the apical-basal polarity. We then discuss the specific roles of RHO and ROCK as essential regulators of TE formation. RHO and ROCK modulate the actomyosin cytoskeleton, apical-basal polarity, intercellular junctions, and HIPPO signaling, thereby orchestrating the epithelialization and gene expressions in TE. Knowledge of the molecular mechanisms underlying TE formation is crucial for assisted reproductive technologies in human and farm animals, as it provides foundation to help improve procedures for embryo handling and selection to achieve better reproductive outcomes.
滋养层（TE）是胎盘哺乳动物着床前发育过程中最先分化的组织。它构成囊胚的外层上皮细胞，负责孵化、子宫附着和胎盘形成。因此，它的形成是使哺乳动物胎生的关键初始步骤。在这里，我们首先描述了在形态和分子水平上 TE 形成的一般特征。拟胚层细胞通过建立顶端-基底细胞极性、细胞间连接、微腔和渗透梯度，形成一个封闭膨胀的充满液体的腔的上皮层。一组独特的基因在 TE 中表达，这些基因编码在着床时发育胎盘滋养层所必需的转录因子。TE 特异性基因表达受 HIPPO 信号通路的抑制驱动，而 HIPPO 信号通路的抑制依赖于顶端-基底极性的预先建立。然后，我们讨论了 RHO 和 ROCK 作为 TE 形成的必需调节因子的具体作用。RHO 和 ROCK 调节肌动球蛋白细胞骨架、顶端-基底极性、细胞间连接和 HIPPO 信号通路，从而协调 TE 中的上皮化和基因表达。了解 TE 形成的分子机制对于人类和农场动物的辅助生殖技术至关重要，因为它为帮助改善胚胎处理和选择程序以实现更好的生殖结果提供了基础。
