PP015. Differential expression of Nrf2 and VEGF in human placental beds from normal and pregnancies complicated with preeclampsia and IUGR

N Kweider; W Rath; B Huppertz; C J Wruck; G Jumakuliev; R Beckmann; T Pufe; M Kadyrov

doi:10.1016/j.preghy.2012.04.126

PP015. Differential expression of Nrf2 and VEGF in human placental beds from normal and pregnancies complicated with preeclampsia and IUGR

Pregnancy Hypertens. 2012 Jul;2(3):248-9. doi: 10.1016/j.preghy.2012.04.126. Epub 2012 Jun 13.

Authors

N Kweider¹, W Rath², B Huppertz³, C J Wruck¹, G Jumakuliev⁴, R Beckmann¹, T Pufe¹, M Kadyrov¹

Affiliations

¹ Department of Anatomy and Cell Biology, RWTH Aachen University, Germany.
² Department of Obstetrics and Gynaecology, University Hospital RWTH, Aachen, Germany.
³ Department of Cell Biology, Histology and Embryology, Medical University of Graz, Graz, Austria.
⁴ Department of Pathology, Ashgabat, Turkmenistan.

PMID: 26105338
DOI: 10.1016/j.preghy.2012.04.126

Abstract

Introduction: Impaired trophoblast invasion into the uteroplacental arteries is accompanied with an evidence of oxidative stress in the extravillous trophoblast in preeclampsia complicated with IUGR.

Objectives: Preeclampsia is characterised by increased lipid oxidation and diminished antioxidant capacity; recently, we have shown that PE is associated with an increased expression of the nuclear factor erythroid 2-related factor 2 (Nrf2) in villous cytotrophoblast. A possible relationship between the vascular endothelial growth factor (VEGF) and Nrf2 was established in vitro and the activation of Nrf2 pathway could lead to upregulation of VEGF synthesis through the induction of Nrf2-dependent Heme oxygenase-1 (HO-1). In this study the expression of Nrf2 and VEGF was determined in the interstitial and intramural extravillous trophoblast in normal pregnancies and those complicated by preeclampsia and intra-uterine growth restriction (IUGR).

Methods: Full-thickness uterine tissues were obtained from caesarean hysterectomies performed in 5 healthy normotensive women delivering term infants and from 5 women with severe early-onset preeclampsia and IUGR (29-34 week's gestation). The interstitial and intramural trophoblasts were studied by immunohistochemical analysis of paraffin sections stained with anti VEGF and anti Nrf2.

Results: Cases suffering from preeclampsia with IUGR were characterised by reduced invasion of extravillous trophoblast into uteroplacental arteries in the endometrial and myometrial segments. In addition, these cells showed an increased expression of Nrf2 in the pathological sections. The overexpression of Nrf2 in cases with preeclampsia was associated with restricted expression of VEGF in these cells compared to controls.

Conclusion: Our data suggest that besides villous cytotrophoblast, also the extravillous trophoblast is a source of Nrf2-dependent genes. VEGF deficiency may cause higher oxidative stress in extravillous trophoblast in cases with preeclampsia with IUGR. The resulting reduced basal defence against oxidative stress and the higher vulnerability to oxidative damage may play a role in the limited trophoblast invasion into uteroplacental arteries in cases suffering from early onset preeclampsia and IUGR.