Role of a fetal defence mechanism against oxidative stress in the aetiology of preeclampsia.
OBJECTIVE
Increasing evidence suggests that oxidative stress may play a key role in the aetiology of preeclampsia (PE). The aim of this study was to elucidate the placental defence mechanisms employed against oxidative stress and, in particular, the specific role of nuclear factor erythroid 2-related factor 2 (Nrf2).


RESULTS
Expression of Nrf2 in third-trimester placental tissue was compared in preeclamptic and normal gestation-matched controls. PE was associated with increased Nrf2 activity within cytotrophoblastic nuclei. Nrf2 expression was restricted to proliferative and early post-proliferative cytotrophoblast only. Syncytiotrophoblast was immunonegative for Nrf2 in both controls and preeclamptic placentas.


CONCLUSIONS
Nrf2 is exclusively active within cytotrophoblast, strongly suggesting that these cells are the origin of Nrf2-dependent gene products. Syncytiotrophoblast is transcriptionally inactive; therefore in times of oxidative stress essential cytoprotective enzymes must be derived from the cytotrophoblast. Excessive cytotrophoblastic turnover causes disproportionate release of toxic placental factors, manifesting as PE and endangering maternal health. Increased cytotrophoblastic proliferation/fusion could thus be interpreted as a fetal defence mechanism, initiated in response to the requirements of vulnerable syncytiotrophoblast. We therefore propose a direct relationship between fetal defence against oxidative stress and consequent placental toxicity as part of the aetiology of this complex maternal disease.
Wruck
Christoph Jan
CJ
Department of Anatomy and Cell Biology, RWTH Aachen University, Aachen, Germany. cwruck@ukaachen.de
Huppertz
Berthold
B
Bose
Patrick
P
Brandenburg
Lars-Ove
LO
Pufe
Thomas
T
Kadyrov
Mamed
M
D000328:Adult; D016022:Case-Control Studies; D049109:Cell Proliferation; D003674:Defense Mechanisms; D005260:Female; D005333:Fetus / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D010920:Placenta / Q000378:metabolism; D011225:Pre-Eclampsia / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology*; D011247:Pregnancy; D011263:Pregnancy Trimester, Third / Q000502:physiology; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism
D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human