Introduction

Oxidative stress of the placenta is a key element in the pathogenesis of pre-eclampsia, although its precise contribution remains uncertain (Hubel, 1999; Redman and Sargent, 2000). The aim of this chapter is to address the origin of that oxidative stress and, as the title suggests, to consider the effects of different oxygen concentrations on placental tissues. In the past it has widely been assumed that the vascular abnormalities in the endometrial arteries of women with pre-eclampsia result in reduced placental perfusion, and hence chronic hypoxia within the feto-placental unit. More recently, the converse has been proposed, and that in pre-eclampsia associated with intrauterine growth restriction (IUGR) the placenta is in fact hyperoxic due to less oxygen than normal being extracted from the intervillous space by the smaller fetus (Kingdom and Kaufmann, 1997). Hypoxia and hyperoxia are relative terms, however, and these assessments have of necessity been based on data obtained at the time of delivery, which, in the majority of cases, represents the end-stage of a process that may have been developing over many weeks. It is therefore difficult to separate primary from secondary effects, and to elucidate earlier stages in the pathogenesis of the disorder. The situation is further complicated by the fact that pre-eclampsia varies widely in severity. Late onset pre-eclampsia is often associated with normal birthweight, whereas early onset of the disease is generally linked with IUGR (Douglas and Redman, 1994).

Introduction

Human early placentation is a difficult topic for systematic research due to ethical constraints, the relative inaccessibility of the tissues and the lack of a suitable animal model, yet events taking place lay the foundation for a successful pregnancy. For many years our knowledge had been reliant upon the interpretation of static images of histological material from pregnant hysterectomy or miscarriage samples. The advent of high-resolution ultrasound imaging in the 1980s provided major new impetus, however, for it enabled events to be followed dynamically in vivo with remarkable clarity. Novel findings using this technique prompted a series of physiological investigations that together have led to a radical reappraisal of the environment in which the feto–placental unit develops. Central to this new appreciation is the premise that the human placenta is not fully haemochorial until the start of the second trimester.

The maternal circulation to the human placenta

During the late secretory phase of the menstrual cycle capillaries arising from the distal segments of the spiral arteries form a plexus within the superficial endometrium that connects with the endometrial veins. When the conceptus implants, the invading syncytiotrophoblastic mantle comes into contact with these capillaries, stimulating them to dilate through endothelial proliferation to form sinusoids, before finally breaking into them (Hertig et al. 1956, Carter 1997). As a result communications are established with the developing lacunae of the trophoblast mantle, the forerunners of the intervillous space, and maternal erythrocytes can be observed in these cavities.