Geburtshilfe Frauenheilkd 2011; 71 - G_20
DOI: 10.1055/s-0031-1286419

Endothelin/endothelin receptor system is upregulated in preeclampsia with or without fetal growth restriction in contrast to gestational diabetes

M Dieber-Rotheneder 1, S Beganovic 1, M Fellner 1, U Lang 1, G Desoye 1, M Cervar-Zivkovic 1
  • 1Department of Obstetrics & Gynaecology, Medical University of Graz, Austria

Introduction:

In addition to its vasoregulative function, in the human placenta endothelin-1 (ET-1) also regulates cell differentiation, proliferation, invasion and apoptosis. ET-1 effects are signaled through two receptor subtypes ETR-A and ETR-B. We tested the hypothesis that the expression of ET-1 and ETRs is altered in preeclampsia (PE), fetal growth restriction (FGR) and in gestational diabetes (GDM) and differs between early (gestational week ≤34) and late (GW >34) third trimester pregnancies.

Methods:

The study included women (GW 28–41) with PE (blood pressure >140/90mmHg, protein >300mg/24hrs; n=16), with FGR (<10th birthweight centile and pathological umbilical blood flow; n=7) and PE+FGR (n=5) and with GDM (±insulin treatment n=21), as well as age-matched controls (n=20). ET-1, ETR-A and ETR-B mRNA and ETR-A and ETR-B protein were quantified in placental tissues by real-time PCR and immunoblotting.

Results:

Table 1: mRNA expression in third trimester pregnancies: – Fold changes versus age-matched controls (p-values)

ETR-A

GW ≤ 34

ETR-B

ET-1

ETR-A

GW >34

ETR-B

ET-1

PE

2.6 (0.04)

3.0 (0.01)

3.5 (0.01)

0.6 (0.05)

2.0 (0.02)

0.4 (0.05)

PE+FGR

5.1 (0.05)

3.4 (0.04)

6.9 (0.003)

-

-

-

FGR

n.s

n.s.

3.8 (0.02)

0.6 (0.05)

n.s.

n.s.

GDM

-

-

-

0.5 (<0.001)

0.8 (0.05)

0.4 (<0.001)

-: not determined, because no material available, n.s.: not significant

In early third trimester pregnancies ETR-A protein was upregulated (+26%) only in PE. There were no changes in ETR-B protein. In late third trimester pregnancies ETR-A (-17%) and ETR-B protein (-33%) were downregulated in GDM. ETR-B protein was also downregulated in FGR (-23%) and PE (-35%).

Discussion:

The upregulation of the ET/ETR system in PE is correlated with the severity of the disease: mild-late<severe-early<PE+FGR). The ET/ETR system is downregulated in GDM.

(Grants: 12243, Jubilee Funds, Austrian National Bank and Kulturamt Stadt Graz)