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Placental Oxidative Stress: From Miscarriage to Preeclampsia

Department of Anatomy, University of Cambridge, Cambridge; Academic Department of Obstetrics and Gynaecology Royal Free and University College London Medical School, London, United Kingdom; gib2{at}cam.ac.uk

Eric Jauniaux, MD, PhD

Department of Anatomy, University of Cambridge, Cambridge; Academic Department of Obstetrics and Gynaecology Royal Free and University College London Medical School, London, United Kingdom

Objective: To review the role of oxidative stress in two common placental-related disorders of pregnancy, miscarriage and preeclampsia.

Methods: Review of published literature.

Results: Miscarriage and preeclampsia manifest at contrasting stages of pregnancy, yet both have their roots in deficient trophoblast invasion during early gestation. Early after implantation, endovascular trophoblast cells migrate down the lumens of spiral arteries, and are associated with their physiological conversion into flaccid conduits. Initially these cells occlude the arteries, limiting maternal blood flow into the placenta. The embryo therefore develops in a low oxygen environment, protecting differentiating cells from damaging free radicals. One embryogenesis is complete, the maternal intervillous circulation becomes fully established, and intraplacental oxygen concentration rises threefold. Onset of the circulation is normally a progressive periphery-center phenomenon, and high levels of oxidative stress in the periphery may induce formation of the chorion laeve. If trophoblast invasion is severly impaired, plugging of the spiral arteries is incomplete, and onset of the maternal intervillous circulation is premature and widespread throughout the placenta. Syncytiotrophoblastic oxidative damage is extensive, and likely a major contributory factor to miscarriage. Between these two extremes will be found differing degrees of trophoblast invasion compatible with ongoing pregnancy but resulting in deficient conversion of the spiral arteries and an ischemia-reperfusion-type pehnomenon. Placental perfusion will be impaired to a greater or lesser extent, generating commensurate placental oxidative stress that is a major contributory factor to preeclampsia.

Conclusion: Miscarriage, missed miscarriage, and early- and late-onset preeclampsia represent a spectrum of disorders secondary to deficient trophoblast invasion.

Key Words: Oxidative stress • placenta • pregnancy • miscarriage • preeclampsia

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