Epithelial to mesenchymal transition (EMT) of feto-maternal reproductive tissues generates inflammation: a detrimental factor for preterm birth

Human pregnancy is a delicate and complex process where multiorgan interactions between two independent systems, the mother, and her fetus, maintain pregnancy. Intercellular inter-actions 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-asso-ciated tissue systems that use EMT, and MET are the fetal mem-brane (amniochorion) amnion epithelial layer and cervical epi-thelial 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 oxida-tive 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 deli-very 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 preg-nancy 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 tran-sitions 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 en-vironment to cause enhancement of uterine inflammation. [BMB Reports 2022; 55(8): 370-379]

Automated summary

Human pregnancy is a complex process characterized by interactions between the mother and fetus. Cells undergo cyclic transitions, known as epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET), to enable tissue remodeling. Maintaining the balance between EMT and MET is crucial, and it is regulated by hormones such as progesterone. Disturbances in these transitions can lead to adverse pregnancy outcomes. Understanding the biomolecular processes involved in cyclic EMT-MET is important for reducing the risk of complications such as preterm birth.