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Human Reproduction Update Advance Access published online on May 8, 2006
Human Reproduction Update, doi:10.1093/humupd/dml016
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© The Author 2006. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org
Received January 20, 2006
Revised March 14, 2006
Accepted March 21, 2006

Article

Placental-related diseases of pregnancy: involvement of oxidative stress and implications in human evolution

Eric Jauniaux 1 *, Lucilla Poston 2, and Graham J. Burton 3

1 Department of Obstetrics and Gynaecology, University College London Medical School, 86-96 Chenies Mews, London WC1E 6HX, UK
2 Maternal and Fetal Research Unit, Kings College London, London
3 Department of Anatomy, University of Cambridge, Cambridge, UK

* To whom correspondence should be addressed.
Eric Jauniaux, E-mail: e.jauniaux{at}ucl.ac.uk


  Abstract

Miscarriage and pre-eclampsia are the most common disorders of human pregnancy. Both are placental-related and exceptional in other mammalian species. Ultrasound imaging has enabled events during early pregnancy to be visualized in vivo for the first time. As a result, a new understanding of the early materno-fetal relationship has emerged and, with it, new insight into the pathogenesis of these disorders. Unifying the two is the concept of placental oxidative stress, with associated necrosis and apoptosis of the trophoblastic epithelium of the placental villous tree. In normal pregnancies, the earliest stages of development take place in a low oxygen (O2) environment. This physiological hypoxia of the early gestational sac protects the developing fetus against the deleterious and teratogenic effects of O2 free radicals (OFRs). In miscarriage, development of the placento-decidual interface is severely impaired leading to early and widespread onset of maternal blood flow and major oxidative degeneration. This mechanism is common to all miscarriages, with the time at which it occurs in the first trimester depending on the aetiology. In contrast, in pre-eclampsia the trophoblastic invasion is sufficient to allow early pregnancy phases of placentation but too shallow for complete transformation of the arterial utero-placental circulation, predisposing to a repetitive ischaemia-reperfusion (I/R) phenomenon. We suggest that pre-eclampsia is a three-stage disorder with the primary pathology being an excessive or atypical maternal immune response. This would impair the placentation process leading to chronic oxidative stress in the placenta and finally to diffuse maternal endothelial cell dysfunction.

Keywords: fetus/miscarriage/oxygen/placenta/pre-eclampsia.
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