Role of a fetal defence mechanism against oxidative stress in the aetiology of preeclampsia

Abstract

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.