title: Anatomical studies of the fetoplacental circulation in pregnancies complicated by growth restriction
Creators: name: Macara, Lena Mary
Publisher: name: University of Glasgow
Year: 1995
Subjects: subject: Physiology, Obstetrics.

description: Severe intrauterine growth restriction (IUGR) is recognised to be a major cause of perinatal morbidity and mortality. Identifying the fetus that is truly growth restricted and therefore compromised, from the one that is simply genetically small and not at risk is difficult. Recent work using umbilical artery (UA) Doppler waveform studies have shown that a reduction in the diastolic component of the UA Doppler waveform correlates strongly with poor perinatal outcome. Since this technique can be used to reliably distinguish the truly growth restricted fetus at risk, it is imperative, if we are to understand the pathophysiology of severe IUGR, that the mechanisms by which abnormal Doppler waveforms arise is established. The elaboration pattern of blood vessels within stem villi from IUGR and gestationally age- matched control placentas, was first evaluated by measuring the diameter of 600 vessel profiles, identified by the antibody anti-a smooth muscle actin, within stem villi from randomly chosen areas of placental tissue. The vessels diameters, ranging from 10-160muM, were plotted in 15muM bands and the two groups compared. There was no significant difference in the mean vessel diameter or in the distribution of vessel diameters in the IUGR and gestational age-matched control placentas. Simultaneously, the mean volume of all classes of villous tissue was calculated. There was significantly less villous tissue in the IUGR placentas than in the matched control placentas. This was the result of a selective reduction in the volume of peripheral (intermediate and terminal) villi in the IUGR placentas. Having identified a quantitative difference in the volume of peripheral villi, scanning electron microscopy (SEM) was used to examine the three-dimensional structure of these villi and the blood vessels within them using vascular and villous tissue casts from pregnancies complicated by severe IUGR and normal preterm controls. The peripheral vascular network of capillaries was noted to be distinctly abnormal in the IUGR placentas. Fewer vessels were identified and when present, these resembled elongated drainpipes. This was in contrast to the normal preterm control vascular casts which were characterised by multiple capillary loops comprised of short, coiled, highly branched, networks with sinusoidal dilatations. Similarily, the peripheral villi of the IUGR placentas were abnormal. Terminal villous "buds", which provide a large syncytial surface area for materno-fetal exchange, were rarely identified. In contrast, the terminal villi of the IUGR placentas, like the vessels within them, resembled narrow tubes. The ultrastastructure of these abnormal terminal villi was then determined using transmission electron microscopy (TEM) and compared with the ultrastructure of normal gestational age- matched teminal villi. The terminal villi from the IUGR placentas were significantly smaller in diameter than their preterm counterparts. In addition, there was an increased number of syncytial nuclei, fewer cytotrophoblast nuclei, thickening of the basement membranes and an increase in the number of collagen fibres and basal lamina like material within the villous stroma. To verify these findings and establish if the reduction in cytotrophoblast cell nuclei number was due to increased turnover or depleted proliferation, the samples were examined with the proliferation marker MIB-1. After correcting for the volume of villous tissue present, this confirmed that there were significantly fewer proliferating cytotrophoblast cells in the IUGR placentas than in normal preterm controls. Likewise using antibodies directed against individual collagen types I, II, III, IV, V, laminin and fibronectin the increase in stromal collagen in the IUGR placental villi was confirmed and recognised to result from increased staining for collagens I, III, IV and laminin. Together these data indicate that primary vascular and villous development is abnormal in placentas from pregnancies complicated by IUGR and abnormal Doppler. As a result, though the total number of stem villous vessels may be reduced, the pattern of their distribution is identical to that seen in normal preterm controls. However, quantitative and qualitative differences were seen in the peripheral villi of the IUGR placentas, the major site of gas and nutrient exchange. The alterations observed may explain both the metabolic adaptation of the IUGR fetus and the Doppler UA abnormalities seen in affected pregnancies. The regulation and expression of angiogenic and villous growth factors in placental development therefore requires urgent attention.