Physiological role of metalloproteinases during pregnancy

The degradation of proteins and connective tissue from extracellular matrix can be a crucial event for tissues in intense remodeling process, with proteases as mediators called matrix metalloproteinases (MMPs). Pregnancy is a very peculiar event in which the uterus undergoes intense morphophysiological modifications, especially related to vascular remodeling and angiogenesis, as well as trophoblast invasion, which occurs in early pregnancy period until reaching maternal spiral arteries and replacing the endothelium forming the endovascular-trophoblast. Such vascular modifications ensure the high-flow and low-pressure blood supply to the developing fetus, which in turn requires more and more space, causing the uterus to become enlarged and distended. In this context, an orchestrated regulation of MMPs and their endogenous inhibitors - such as tissue inhibitors of metalloproteinases (TIMP) - are essential for proper gestational development. The disordered uteroplacental remodeling is associated with several obstetric complications, such as placenta accreta, fetal growth restriction, abortion, preterm delivery and pre-eclampsia. Studies of MMPs involved in the uterine remodeling process and their relationship to local maternal immune cells, as well as fetal trophoblastic cells, still represent a very promising field of research, since the elucidation of the involved processes can boost the development of strategies to prevent complications in woman's health, obstetrics and for consequences in offspring adulthood.