Epidermal growth factor receptors and human placenta

Abstract

s: European Placenta Group/Rochester Trophoblast Joint Conference EPIDERMAL GROWTH FACTOR RECEPTORS AND HUMAN PLACENTA C. V. Rao & N. Chegini (University of Louisville School of Medicine, KY, USA) 47I Term human placenta is one of the richest sources of receptors for epidermal growth factor (EGF). EGF is present in maternal and fetal circulation and in amniotic fluid. However, the source of EGF in these compartments is not known. The EGF receptors are present primarily in syncytiotrophoblasts. By light microscope autoradiography, we have found that these receptors were high at mid pregnancy and decreased towards term. This is the opposite of biochemical binding measurements. The latter observations can be explained by the presence of more connective tissue in placental cotyledons at mid term compared with term pregnancy. The receptors are enriched in microvillous plasma membranes, which are exposed to maternal circulation. The receptors are also found in basolateral plasma membranes, which are in close proximity to fetal blood capillaries. Since EGF may not cross the placenta, maternal EGF may influence syncytiotrophoblast function by binding to receptors in microviilous plasma membranes, whereas fetal EGF may also influence syncytiotrophoblast function via receptors in basolateral plasma membranes. The EGF in amniotic fluid presumably interacts with receptors in fetal membranes and decidua. In addition to the two outer cell surface membranes of syncytiotrophoblasts, EGF binding and EGF responsive kinase activities were also found in lysosomes, rough and smooth endoplasmic reticulum and Golgi elements. Quantitative electron microscope autoradiographic studies revealed that 12SI-EGF internalizes and associates with all of the above intracellular organelles in addition to nuclei. While the placental 125I-EGF binding differed among some pregnancy states, fetal membrane 12SI-EGF binding was similar in all the pregnancy states. This suggested that placental and fetal membrane EGF receptors are regulated differently. PERMEABILITY OF THE IN SITU PERFUSED RAT PLACENTA N. Robinson, R. Jenkins, P. Thomas & C. Sibley (St Mary's Hospital, Manchester, UK) A method for the in situ perfusion of the rat placenta has recently been developed. This preparation has allowed simple measurement of the permeability of the rat placenta to a range of hydrophilic molecules as follows: At 2I + i days of gestation, animals were anaesthetized with sodium thiobutabarbital and, after laparotomy, the uterus was exposed and the fetal circulation of one of the placentae was perfused, via an umbilical artery cannula with a modified Krebs' Ringer, at o.5 ml/min. A range of radiolabelled hydrophilic molecules, of increasing molecular size, were injected as a bolus into the mother and three samples of maternal plasma were taken at to--min intervals for measurement of radioactivity whilst fetal side perfusate was collected at 4min intervals from a cannula in the umbilical vein. The permeability surface area product (PS) was calculated as: PS (/d/rain/g)= (venous perfusate radiolabel concentration • flow rate) (mean maternal plasma radiolabel concentration x placental weight). The ratio of PS/D, where D is the diffusion coefficient in water of the particular molecule, was independent of molecular size for 14C-mannitol, 51CrEDTA and 14C/3H-inulin, whilst the PS/D for ~25Ialbumin suggested steric hindrance of this molecule. By contrast, the PS/D of 22Na+, 15.06 + i.oocm/g suggested additional non-diffusional transport. These results are close to those obtained in the intact rat placenta, and therefore, unlike the guinea pig, perfusion in the rat does not appear to be associated with increased placental porosity.