Current model systems for the study of preeclampsia

Abstract

Preeclampsia (PE) is a pregnancy complex disease, distinguished by high blood pressure and proteinuria, diagnosed after the 20th gestation week. Depending on the values of blood pressure, urine protein concentrations, symptomatology, and onset of disease there is a wide range of phenotypes, from mild forms developing predominantly at the end of pregnancy to severe forms developing in the early stage of pregnancy. In the worst cases severe forms of PE could lead to systemic endothelial dysfunction, eclampsia, and maternal and/or fetal death. Worldwide the fetal morbidity and mortality related to PE is calculated to be around 8% of the total pregnancies. PE still being an enigma regarding its etiology and pathophysiology, in general a deficient trophoblast invasion during placentation at first stage of pregnancy, in combination with maternal conditions are accepted as a cause of endothelial dysfunction, inflammatory alterations and appearance of symptoms. Depending on the PE multifactorial origin, several in vitro, in vivo, and in silico models have been used to evaluate the PE pathophysiology as well as to identify or test biomarkers predicting, diagnosing or prognosing the syndrome. This review focuses on the most common models used for the study of PE, including those related to placental development, abnormal trophoblast invasion, uteroplacental ischemia, angiogenesis, oxygen deregulation, and immune response to maternal-fetal interactions. The advances in mathematical and computational modeling of metabolic network behavior, gene prioritization, the protein-protein interaction network, the genetics of PE, and the PE prediction/classification are discussed. Finally, the potential of these models to enable understanding of PE pathogenesis and to evaluate new preventative and therapeutic approaches in the management of PE are also highlighted. Impact statement This review is important to the field of preeclampsia (PE), because it provides a description of the principal in vitro, in vivo, and in silico models developed for the study of its principal aspects, and to test emerging therapies or biomarkers predicting the syndrome before their evaluation in clinical trials. Despite the current advance, the field still lacking of new methods and original modeling approaches that leads to new knowledge about pathophysiology. The part of in silico models described in this review has not been considered in the previous reports.

The diagnosis values of serum STAT4 and sEng in preeclampsia

“…At present, the etiology theories generally include the theory of uterine‐placental ischemia, theory of abnormal blood vessel‐regulating substance, immunological theory, and hereditary theory . Placental ischemia and hypoxia and endothelial dysfunction are recognized as important factors leading to preeclampsia . In pregnancy, the fetus is a homologous allograft, so the process of pregnancy is actually autologous allogenic process.…”

“…26,27 Placental ischemia and hypoxia and endothelial dysfunction are recognized as important factors leading to preeclampsia. [6][7][8][9] In pregnancy, the fetus is a homologous allograft, so the process of pregnancy is actually autologous allogenic process. Under normal conditions, the maternal immune system is balanced, and the preeclampsia patients have a rejection between the placenta and the mother body, which can lead to the invasion of trophoblastic cells and the uterus.…”

“…There are many theories about the pathogenesis of preeclampsia, including the theory of immune imbalance, the theory of oxidative stress, the theory of placental ischemia and hypoxia, the theory of the abnormality of trophoblast invasion, the theory of endothelial cell injury, the theory of genetic susceptibility, the theory of renin‐angiotensin‐aldosterone, dysregulation of coagulation and fibrinolysis system, and theory of nutritional deficiencies, insulin resistance, and environmental factors . These theories are frequently integrated and interrelated with each other.…”

“…the abnormality of trophoblast invasion, the theory of endothelial cell injury, the theory of genetic susceptibility, the theory of renin-angiotensin-aldosterone, dysregulation of coagulation and fibrinolysis system, and theory of nutritional deficiencies, insulin resistance, and environmental factors. [6][7][8][9] These theories are frequently integrated and interrelated with each other. For the understanding of preeclampsia, it is considered to be a placenta-derived disease, a series of syndromes caused by placental ischemia and hypoxia; it can also be considered as a maternal disease, that is, placental development is normal.…”

Acute Kidney Injury in Pregnancy: The Need for Higher Awareness. A Pragmatic Review Focused on What Could Be Improved in the Prevention and Care of Pregnancy-Related AKI, in the Year Dedicated to Women and Kidney Diseases

“…Whatever the causes, even if proteinuria, which is one of the hallmarks of PE, is usually considered as a marker of glomerular involvement, and podocyte damage is regarded as a main pathogenetic pathway, tubular damage is probably more common than previously considered [ 46 ]. In PE and all the kidney structures may be affected, ultimately resulting in p-AKI, the common pathway of other pregnancy- related noxae, such as sepsis and shock [ 47 , 48 , 49 , 50 ] ( Table 3 , Figure 3 ).…”