Changes in the cervical extracellular matrix during pregnancy and parturition

Abstract

The key function of the uterine cervix to maintain pregnancy is biochemically characterized by an increased synthesis of proteins (e.g., collagen), proteoglycans, and glycoproteins (e.g., fibronectin) as well as by defined interactions between these components of the extracellular matrix. In contrast to the slow phase of the cervical ripening process in late pregnancy, cervical dilatation during parturition requires the rapid production and action of catabolic enzymes leading mainly to collagen degradation and changes in its architecture but also to degradation of other fundamental matrix proteins. Evidence suggests that an increased production of TNF-alpha and IL-1 beta, e.g., induces a rise in the expression of endothelial adhesion molecules with subsequent extravasation of neutrophils into the cervical stroma and that the chemotaxis and degranulation of these cells is triggered by an increased concentration of IL-8. Rising concentrations of hyaluronan at this time have been considered as potent inducers of IL-1 beta and TNF-alpha synthesis by various leukocyte populations. The increase in IL-6 synthesis stimulates prostaglandin and leukotriene production causing dilatation of cervical vessels and further promoting the extravasation of leukocytes. The proteases released after degranulation of neutrophils encounter an already destabilized collagenous fiber network. Since a sustained action of proteases may lead to severe tissue damage, this process is strictly limited in time and is controlled by increasing concentrations of tissue inhibitors of protease in the lower uterine segment immediately after delivery. The clinical consequences of this basic research is to develop new concepts in a more causal treatment of cervical pathology during pregnancy and parturition.