The placenta in preeclampsia

Abstract

The root cause of preeclampsia is the placenta. Preeclampsia begins to abate with the delivery of the placenta and can occur in the absence of a fetus but with the presence of trophoblast tissue with hydatidiform moles. In view of this, study of the placenta should provide insight into the pathophysiology of preeclampsia. In this presentation we examine placental pathological and pathophysiological changes with preeclampsia and fetal growth restriction (FGR). It would seem that this comparison should be illuminating as both conditions are associated with similarly abnormal placentation yet only in preeclampsia is there a maternal pathophysiological syndrome. Similar insights about early and late onset preeclampsia should also be provided by such information.We report that the placental abnormalities in preeclampsia are what would be predicted in a setting of reduced perfusion and oxidative stress. However, the differences from FGR are inconsistent. The most striking differences between the two conditions are found in areas that have been the least studied. There are differences between the placental findings in early and late onset preeclampsia but whether these are qualitative, indicating different diseases, or simply quantitative differences within the same disease is difficult to determine.We attempt to decipher the true differences, seek an explanation for the disparate results and provide recommendations that we hope may help resolve these issues in future studies.

Figure 1. A Schematic Representation of Human Placentation

Based on the available data it appears that the abnormal modification of the maternal vessels supplying the intervillus space is the same in preeclampsia and fetal growth restriction (FGR) without preeclampsia. The placental changes are similar in early onset preeclampsia and FGR (particularly when early onset preeclampsia is accompanied by FGR). The consequences of the reduced nutrient and oxygen delivery and the increased flow of blood delivered to the intervillus space are similar in FGR and preeclampsia but not identical. In FGR, placental inflammation is increased, as is apoptosis. These changes are also present in preeclampsia but may be more severe and are also accompanied by necrosis that is not as prevalent in FGR. Oxidative stress, as indicated by increased reactive oxygen species (ROS) and reduced antioxidants is present in the periphery of the placenta where maternal blood supply is reduced compared with the central region, in either normal or pathological conditions. The degree of oxidative stress is more in FGR than normal pregnancy and even greater in preeclampsia. Data on the response to reduced oxygen in FGR is not consistent (indicated by ??). Hypoxia and the response to hypoxia may be less in FGR than preeclampsia. In response to apoptosis, increased pressure and necrosis, fragments of syncitiotrophoblast are released into the maternal circulation, which are both increased in quantity, and qualitatively different in preeclampsia (necrotic particles indicated by black circles are greater with preeclampsia) compared with normal pregnancy or FGR. It is postulated (?? and dotted line) that apoptosis, or inflammatory and proangiogenic factors from syncitiotrophoblast in normal and pathological conditions regulate placental vascularization. In both FGR and preeclampsia the fetal vasculature responds to reduce the villous surface area. Whether this is quantitatively and qualitatively different in the two conditions is not established, but only in preeclampsia has spotty placental vascular development resulting in an abnormally shaped placenta been reported. The final fetal result is by definition reduced fetal growth in FGR but this is not universally present even with early onset preeclampsia.