## 5 Collagen Type I and III Turnover in Normal Pregnancy  
Collagen types I and III are the main proteins involved in the structure of the uterine wall. As the uterus grows during pregnancy, there is an intensified collagen turnover. It is well known that the uterine collagen structure has been shown to be disturbed in women with pre-eclampsia. Amino-terminal and carboxy-terminal propeptides of collagen type I and III play a central role in this process [24]. The human uterus is composed of a fibrous tissue framework consisting mainly of collagen types I and III [25]. It is, therefore, possible that in hypertensive disorders in pregnancy these collagens (which are mainly responsible for the coherence and supportive strength of the uterus) could be affected. Controlled collagenolysis and/or changes in collagen cross-linking will be needed to meet the demand of the growing uterine content to expand. As the uterus grows during pregnancy there is a high production and turnover of collagen proteins [26]. Collagen types I and III are major components of human cervical uterine connective tissue. During pregnancy, a remodeling of the cervical connective tissue takes place, with decreases in the concentrations of collagen and proteoglycans concomitant with an increase in the collagenolytic activity [27; 28; 29]. 70% decrease in the amount of collagen and the change in its organization is observed [30; 31]. In abnormal conditions such as preeclampsia and gestational hypertension, the blood flow to both placenta and foetus is disturbed, favouring a microcirculatory ischaemia. Altered extracellular matrix turnover with MMP/TIMP dysbalance play a crucial role in these pathological processes [32; 33]. Impaired Collagen Type I and III Turnover in Preeclampsia--The Role of MMP/TIMP Complex Dysregulation  
Several studies suggest that a key trait of preeclampsia is \"the impaired capacity of the trophoblast to invade the uterine spiral arteries resulting in a poorly perfused fetol placental unit. As a result various factors inducing endothelial dysfunction could be found in circulation of women with preeclampsia\" [34; 35]. Changes in circulatory concentrations and activity of MMPs as well as their endogenous inhibitors, TIMPs, majorly involved in collagen metabolism, led to the consideration of these proteases as key mediators in the pathological features of preeclampsia [36]. Preeclampsia (PE) is one of the most widely seen hypertensive disorders of pregnancy. Data show that preeclampsia complicates about 2-8% of pregnancies worldwide [37]. PE is characterized by the new onset of hypertension (\(\geq\)140/90 mmHg) and proteinuria (0.3 g in a 24 h urine sample) occurring after 20 weeks of gestation [38]. PE is a major cause of maternal and perinatal morbidity and mortality. Despite that fact, it has not been fully studied yet. Preeclampsia is an important pregnancy complication and one of the most common pregnancy disorders. Preeclampsia is characterized by a high blood pressure of mother, often with proteinuria. Fetal growth restriction is also generally seen. There is evidence that, extracellular matrix (ECM) metabolism is altered in the human uterus during preeclampsia. However, little is known about the change in the composition of the collagen in the human uterus during preeclampsia [39; 40]. The human uterine wall consists mainly of collagen types I and III. These proteins play a central role in the stability of tissue structure and the regulation of cell growth and differentiation. The processes of collagen types I and III synthesis and degradation in ECM of human uterus are dynamic and reflect not only healthy, but also complicated pregnancy [41]. Collagen turnover has been shown to be impaired in women with preeclampsia [42]. Early preeclampsia detection is paramount for risk stratification and prevention of further complications. Collagen structure of the uterus has been shown to be impaired in women with preeclampsia. This is a result of MMPs/TIMPs dysregulation interplay.