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

摘要

Aims: Preeclampsia (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 (ET A and ET B) is altered in these pathologies and differs between early (gestational week [GW] ≤ 34) and late (GW 34) third trimester pregnancies. Main methods: The 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, ET A and ET B mRNA and ET A and ET B protein were quantified in placental tissues by real-time PCR and immunoblotting. Key findings: The ET/ETR mRNA system is altered in PE and PE + FGR and GDM. Expression of ET-1, ET A and ET B 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. Significance: Early 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.