Division of Basic and Translational Research, Department of Obstetrics and Gynecology, The University of Texas Medical Branch at Galveston, Galveston 77555-1062, TX, USA.
BMB Rep. 2022 Aug;55(8):370-379. doi: 10.5483/BMBRep.2022.55.8.174.
Human pregnancy is a delicate and complex process where multiorgan interactions between two independent systems, the mother, and her fetus, maintain pregnancy. Intercellular interactions that can define homeostasis at the various cellular level between the two systems allow uninterrupted fetal growth and development until delivery. Interactions are needed for tissue remodeling during pregnancy at both fetal and maternal tissue layers. One of the mechanisms that help tissue remodeling is via cellular transitions where epithelial cells undergo a cyclic transition from epithelial to mesenchymal (EMT) and back from mesenchymal to epithelial (MET). Two major pregnancy-associated tissue systems that use EMT, and MET are the fetal membrane (amniochorion) amnion epithelial layer and cervical epithelial cells and will be reviewed here. EMT is often associated with localized inflammation, and it is a well-balanced process to facilitate tissue remodeling. Cyclic transition processes are important because a terminal state or the static state of EMT can cause accumulation of proinflammatory mesenchymal cells in the matrix regions of these tissues and increase localized inflammation that can cause tissue damage. Interactions that determine homeostasis are often controlled by both endocrine and paracrine mediators. Pregnancy maintenance hormone progesterone and its receptors are critical for maintaining the balance between EMT and MET. Increased intrauterine oxidative stress at term can force a static (terminal) EMT and increase inflammation that are physiologic processes that destabilize homeostasis that maintain pregnancy to promote labor and delivery of the fetus. However, conditions that can produce an untimely increase in EMT and inflammation can be pathologic. These tissue damages are often associated with adverse pregnancy complications such as preterm prelabor rupture of the membranes (pPROM) and spontaneous preterm birth (PTB). Therefore, an understanding of the biomolecular processes that maintain cyclic EMT-MET is critical to reducing the risk of pPROM and PTB. Extracellular vesicles (exosomes of 40-160 nm) that can carry various cargo are involved in cellular transitions as paracrine mediators. Exosomes can carry a variety of biomolecules as cargo. Studies specifically using exosomes from cells undergone EMT can carry a pro-inflammatory cargo and in a paracrine fashion can modify the neighboring tissue environment to cause enhancement of uterine inflammation. [BMB Reports 2022; 55(8): 370-379].
人类妊娠是一个微妙而复杂的过程，在此过程中，两个独立系统（母亲及其胎儿）之间的多器官相互作用维持妊娠。细胞间的相互作用可以定义两个系统之间各种细胞水平的内稳态，从而使胎儿能够不间断地生长和发育，直至分娩。在妊娠期间，胎儿和母体组织层都需要进行组织重塑，细胞发生上皮-间充质转化（EMT）和间充质-上皮转化（MET）的循环转变是实现这一过程的必要条件。帮助组织重塑的机制之一是细胞发生过渡，其中上皮细胞经历从上皮到间充质（EMT）的周期性转变，然后再从间充质到上皮（MET）的转变。在此将回顾两种主要的妊娠相关组织系统，即胎儿膜（羊膜绒毛膜）羊膜上皮层和宫颈上皮细胞，它们都利用 EMT 和 MET。EMT 通常与局部炎症有关，这是一个平衡的过程，有助于组织重塑。循环转变过程很重要，因为 EMT 的终末状态或静止状态会导致炎症性间充质细胞在这些组织的基质区域积聚，并增加局部炎症，从而导致组织损伤。决定内稳态的相互作用通常受到内分泌和旁分泌介质的控制。妊娠维持激素孕酮及其受体对于维持 EMT 和 MET 之间的平衡至关重要。足月时宫内氧化应激增加会迫使 EMT 进入静态（终末）状态，并增加炎症，这是破坏维持妊娠的内稳态以促进胎儿分娩的生理过程。然而，导致 EMT 和炎症过早增加的情况可能是病理性的。这些组织损伤通常与不良妊娠并发症有关，如早产胎膜早破（pPROM）和自发性早产（PTB）。因此，了解维持循环 EMT-MET 的生物分子过程对于降低 pPROM 和 PTB 的风险至关重要。可以作为旁分泌介质参与细胞过渡的细胞外囊泡（40-160nm 的外泌体）携带各种货物。外泌体可以携带多种生物分子作为货物。特别是使用经历 EMT 的细胞的外泌体进行的研究可以携带促炎货物，并以旁分泌方式修饰邻近组织环境，导致子宫炎症增强。[BMB 报告 2022；55(8):370-379]。
