Although pre-eclampsia (PE) is often associated with fetal hypoxia, hypertension and/or disturbed function of the fetal circulation, the effect of these altered hemodynamic parameters on the structure and composition of umbilical vessels has not been systematically investigated before. Therefore, this study focuses on PE-associated changes of the elastic fibre system in umbilical cord vessels investigated by light and electron microscopy, immunocytochemistry and biochemistry. In umbilical cord veins, no changes in thickness of the vessel wall or of any sublayer were observed. However, the internal elastic lamina of the veins was split in 80% of the PE-group in contrast to 20% in uncomplicated pregnancies. This effect was significant (alpha <0.01) from 36 weeks of gestation onwards. In umbilical cord arteries, the entire arterial vessel wall was found to be 15% thicker in PE than in uncomplicated pregnancies. The enlargement was caused by an increase of both the tunica intima and tunica media. The thickening of the tunica intima was attributed to a migration of smooth muscle cells towards the endothelium, accompanied by a splitting of the internal elastic lamina. Compared to uncomplicated pregnancies, smooth muscle cells of arteries and veins in PE showed a metabolic activation demonstrated by highly dilated endoplasmic reticulum. A semiquantitative score method as well as a quantitative dot blot assay indicated a PE-associated reduction of elastin expression in the arterial vessel walls. In summary, PE obviously induces a decrease of the elastin content accompanied by a thickening of the vessel wall in umbilical cord arteries. This remodeling of the elastic fibre system, together with an increased migration of smooth muscle cells, might represent part of the functional adaptation system of the umbilical cord arteries on the altered hemodynamic conditions in PE.

Hyaluronan (HA), a high molecular weight polysaccharide, is a major component of connective tissue and is thus present in the extracellular matrix of most tissues. Increased serum concentrations have been reported in association with pre-eclampsia and liver malfunction, amongst other disorders. We have performed histochemical investigations with a HA-specific hyaluronic acid binding protein in placentas from uncomplicated pregnancies and from patients with pre-eclampsia. Staining for HA was found in the stroma and blood vessel walls of stem villi in all the placentas investigated. The syncytiotrophoblast and cytotrophoblast cells usually remained unstained. In addition, reactivity for HA was found within and on the surface of intervillous and perivillous fibrinoid deposits. Since fibrinoid deposits are increased in pre-eclampsia, our findings suggest that the increased HA serum concentrations in cases of pre-eclampsia could result from the stroma of the infarcted villi and from the fibrinoid deposits. HA may reach the maternal blood through fibrinoid gaps.

In recent studies we described the presence of elastic-type blood vessels within trunci and rami chorii of human placental stem villi. For systemic and pulmonary hypertension it is known that elastic fibres are enhanced in arteries. The aim of our study was, therefore, to examine whether pre-eclampsia may lead to an increase of elastic tissue fibres in blood vessel walls of placental stem villi and whether there are differences in the thickness of blood vessel walls within these villi when compared to normotensive pregnant women. Twenty-six women with uncomplicated pregnancies and 25 patients with pre-eclampsia were investigated. Unfixed cryostat serial sections were processed for conventional orcein staining and for the demonstration of alpha-actin-immunoreactivity. The intensity of orcein staining of stem villus blood vessel walls was evaluated by a semiquantitative score method. Significant higher intensities of orcein staining (P<0.00001) were calculated for blood vessel walls of placentae with pre-eclampsia. The amount of thick stem villus vessels (>41 microm) increased during pre-eclampsia from 39 gestational weeks onwards. Our study demonstrates that segments of thick blood vessel walls and elastic-type vessel walls are increased in placental stem villi of patients with pre-eclampsia. This reaction may protect the fetal placental vessels and avert an increase of the fetal hypertension.

In previous studies, we have shown that smooth muscle cells and myofibroblast subpopulations of the perivascular stem villous sheath of the human placenta contain focal adhesion plaques and talin immunoreactivity. The close association of these cells to elastic and collagen fibres have led to the assumption of a functional myofibroelastic unit within the perivascular stem villous sheath. Interactions between the extracellular matrix and smooth muscle cells depend on a variety of structural protein assemblies. In the present study, we examined, by immunocytochemistry, whether the molecular assembly of extracellular matrix proteins and molecules of focal adhesions, known to be essential for signal transduction in smooth muscle cells, are also found in smooth muscle cells of the perivascular stem villous sheath of the human placenta. Vascular and extravascular smooth muscle cells were immunoreactive for alpha-actinin, vinculin, paxillin and tensin, the integrin chains alpha1 and beta1, and the basement membrane components laminin and heparan/-chondroitin sulfate proteoglycan perlecan. pp125(FAK) did not react. In the extracellular matrix of blood vessel walls and the perivascular stem villous sheath, we found immunoreactivity of fibronectin and collagen types I, VI and undulin (collagen type XIV). From our data we conclude that within the perivascular stem villous sheath, there exists a system of signal transduction molecules, indicating a cross talk between the smooth muscle cells of this sheath and their surrounding extracellular matrix.

In a recent study we described an increase of elastic tissue fibres in blood vessel walls of placental stem villi during pre-eclampsia when compared to uncomplicated pregnancies. Furthermore, the thickness of these blood vessel walls was enhanced in pre-eclampsia. Since it is known that elastic tissue fibres increase in systemic hypertension, it may be assumed that the enhancement of elastic tissue fibres in placental stem villi during pre-eclampsia may be induced by the hypertension. To get further insight into this assumption, we examined the amount of elastic tissue fibres in stem villus blood vessels of placentae of pregnancies complicated by intrauterine growth retardation (isolated IUGR, fourteen cases), a disease without hypertension of the mother and such with pre-eclampsia and concomitant IUGR (IUGR+PE, nine cases). Each study group was compared with uncomplicated pregnancies (twenty-six cases). Unfixed cryostat serial sections were processed for conventional orcein staining and for the demonstration of alpha-actin-immunoreactivity. The intensity of orcein staining of stem villus blood vessel walls was evaluated by a semiquantitative score method. Significant lower intensities of orcein staining were calculated for blood vessel walls of placentae of isolated IUGR (P=0.0007) and IUGR+PE (P=0.0039) when compared to uncomplicated pregnancies each. Additionally, the blood vessel wall thickness of stem villi of isolated IUGR (P=0.0081) and IUGR+PE (P=0.0007) was significantly reduced. In comparison to the above mentioned investigation, our results show that, in contrast to isolated pre-eclampsia, elastic tissue fibres are decreased during pregnancies complicated by IUGR, independently of the occurrence of concomitant pre-eclampsia when compared to uncomplicated pregnancies. From our studies it may be considered that the increase of elastic tissue fibres in placentae of patients with isolated pre-eclampsia may be induced by systemic hypertension. Furthermore, our study underline arguments that IUGR may be an independent disease of the fetus.