Insight into the Key Points of Preeclampsia Pathophysiology: Uterine Artery Remodeling and the Role of MicroRNAs

Abstract

Preeclampsia affects about 3–8% of all pregnancies. It represents a complex and multifaceted syndrome with at least several potential pathways leading to the development of disease. The main dogma in preeclampsia is the two-stage model of disease. Stage 1 (placental stage) takes place in early pregnancy and is thought to be impaired placentation due to inadequate trophoblastic invasion of the maternal spiral arteries that leads to reduced placental perfusion and release of numerous biological factors causing endothelial damage and development of acute maternal syndrome with systemic multiorgan failure (stage 2—the onset of maternal clinical symptoms, maternal stage). Recently, in the light of the vast body of evidence, two-stage model of preeclampsia has been updated with a few novel pathways leading to clinical manifestation in the second part of pregnancy. This paper reviews current state of knowledge about pathophysiology of preeclampsia and places particular focus on the recent advances in understanding of uterine artery remodeling alterations, as well as the role of microRNAs in preeclampsia.

Molecular Mechanisms Underlying the Association between Endometriosis and Ectopic Pregnancy

“…They do not translate proteins, but can regulate gene expression by silencing mRNA translation and causing target mRNA degradation [ 97 , 98 ]. There is a vast body of evidence for a crucial role of miRNAs in the development and potential treatment of many diseases, including reproductive health diseases, such as premature ovarian insufficiency (POI), polycystic ovarian syndrome (PCOS) and infertility, as well as pregnancy complications (i.e., preeclampsia and fetal growth restriction) [ 99 , 100 , 101 , 102 , 103 ].…”

Unique Aspects of Human Placentation

“…In a healthy pregnancy, trophoblast invasion extends through the relatively shallow endometrium to the inner third of the myometrium. Shallower invasion leads to inadequate transformation of the spiral arteries, thereby limiting the blood supply to the intervillous space, and is causally associated with fetal growth restriction and preeclampsia [ 1 , 44 ]. Trophoblasts that invade by the interstitial route undergo endoreduplication [ 45 ] and go no deeper than the inner myometrium, where they are found as multinucleate giant cells [ 46 ].…”

Genetic Background of Fetal Growth Restriction

“…In a study performed by Hung et al, FGR was diagnosed in 50.6% of women with early-onset PE and in 25.5% patients with late-onset disease [ 81 ]. Such a high incidence of FGR during PE is related to the very similar pathomechanism of these two pregnancy complications, based on the inadequate trophoblast invasion into maternal spiral arteries and maternal endothelial dysfunction [ 82 , 83 ]. However, it is still under consideration why among women with the same risk factors, some of them develop only FGR and some of them develop PE with or without FGR.…”