Complex expression changes of the placental endothelin system in early and late onset preeclampsia, fetal growth restriction and gestational diabetes

AimsPreeclampsia (PE), fetal growth restriction (FGR) and gestational diabetes mellitus (GDM) are major pregnancy complications affecting maternal and fetal health. The placenta and the vasoconstrictor endothelin-1 (ET-1) have a controlling and mediating role in these conditions. This study tested the hypothesis that the expression of ET-1 and its receptors (ETA and ETB) is altered in these pathologies and differs between early (gestational week [GW] ≤ 34) and late (GW > 34) third trimester pregnancies.Main methodsThe study included 88 women (GW 28-41) with PE (blood pressure > 140/90 mmHg, protein > 300 mg/24 hrs; n = 14), FGR (< 10th birthweight centile and pathological umbilical blood flow; n = 13), PE + FGR (n = 5) and GDM (n = 21), and gestational age-matched controls (n = 35). ET-1, ETA and ETB mRNA and ETA and ETB protein were quantified in placental tissues by real-time PCR and immunoblotting.Key findingsThe ET/ETR mRNA system is altered in PE and PE + FGR and GDM. Expression of ET-1, ETA and ETB is upregulated in early onset PE and PE + FGR with stronger effect in PE + FGR. GDM down regulated ET/ETR mRNA in the placentas in late third trimester of pregnancy. ET/ETR protein is virtually unchanged.SignificanceEarly onset PE (≤ GW34) with or without FGR is associated with increased mRNA expression of the ET/ETR system, while in late onset PE and GDM the opposite effect was observed. This study supports the emerging concept that early and late onset PE are different diseases.