Trophoblast invasion is an essential component of haemochorial placentation and has to be considered in relation to reactive changes in the maternal uterine tissues. Some comparative aspects of human and laboratory rodents are discussed and, although there is an obvious phylogenetic gap between the two, many characteristics of placental development are found to be analogous. Trophoblast growth into the uterus is different in different species: localized trophoblast growth forming a bulky tissue (mouse, rat, hamster) contrasts with a dispersion of independent trophoblastic elements, forming an interstitial invasion (guinea pig, man). In the rat, mouse, hamster and man retrograde intra-arterial trophoblast migration occurs in maternal vessels supplying blood to the developing placenta. Early changes in maternal tissues might influence trophoblast behaviour. Decidualization probably is a key phenomenon, and the relation of decidual necrosis to trophoblast invasion is considered. Some kind of controlled immune response by the mother also may be involved. These considerations apply to stromal or interstitial invasion as well as to intravascular trophoblast migration but, for the latter, haemodynamic factors probably influence tissue reactions.
A series of monoclonal antibodies has been raised against the human choriocarcinoma cell-line, BeWo. Four antigens, Trop-1, -2, -3, and -4, are defined on normal and malignant trophoblast cells. Trop-1 and Trop-2 appear to be specifically expressed on syncytio- and cytotrophoblasts, whereas Trop-3 and Trop-4 are also detected on various tumor cell lines, normal lymphocytes, and monocytes. Anti-Trop-1 and anti-Trop-2 antibodies might prove useful for detection and isolation of fetal trophoblast cells circulating in pregnant women's blood and for diagnosis and therapy in patients having choriocarcinomas and other germ-cell neoplasms.
It is known that renin is present in fetal membranes, with the highest concentration in the chorion laeve (reflected chorion). The purpose of this study was to identify and localize renin in human chorion laeve. Indirect immunofluorescent analysis, using antiserum against pure human kidney renin, revealed a single layer of cells in the chorion with strongly positive fluorescence. The presence of atrophic villi in this layer together with other morphological evidence indicate that the cells which are positive for renin are cytotrophoblasts. Isolated cells were prepared from the chorion by collagenase digestion, followed by filtration and density gradient centrifugation on Percoll. The isolated cells also showed a positive reaction with the immunofluorescent technique. Control experiments with nonimmune serum did not show fluorescent cells. Biochemical analysis using RIA of angiotensin I generated from sheep substrate indicated that most of the renin activity in the isolated cells was present as inactive renin (activated by trypsin). The presence of renin in trophoblastic cells may be of significance in local cardiovascular regulation, events associated with parturition, or pathophysiological manifestations of trophoblastic disease.
A radioimmunoassay was developed to directly assay the presence of transferrin receptors in human tissues. Antisera developed in a goat against purified human placental transferrin binding protein was purified by fractional sodium sulfate precipitation and adsorption against Sepharose-bound transferrin to remove trace anti-transferrin activity. The antisera immunoprecipitates a M 94,000 peptide on I-iodinated syncytial trophoblast membranes from placentae. This polypeptide has been identified previously as the transferrin binding protein of the placenta [Wada, H. G., Hass, P. E. & Sussman, H. H. (1979) J. Biol. Chem. 254, 12629-12635]. A standard curve using purified I-iodinated placental transferrin receptor and various amounts of the purified noniodinated receptor is sensitive from 5 to 900 ng. A reticulocyte-enriched membrane ghost preparation (5% reticulocyte) gives a value of 9.5 μ g of receptor per mg of protein. Normal erythrocyte membrane ghosts show binding (0.57 μ g of receptor per mg of protein) proportional to the amount of reticulocytes normally present in blood (0.5-1.0%). In other tissues in which the transferrin receptor binding has been reported, purified syncytial trophoblastic membranes are found to have 34.5 μ g of receptor per mg of protein, and BeWo cells, a choriocarcinoma cell line, are found to have 15.7 μ g of receptor per mg of protein. In contrast, normal breast tissue, which has no demonstrated transferrin binding, contains only 0.18 μ g of receptor per mg of protein by this method.
Rat giant trophoblast cells contain a factor which stimulates DNA polymerase α derived from trophoblast cells as well as from calf thymus. The factor, which has been partially purified on a glycerol gradient, has an approximate M of 85,000 and is non-dialyzable, heat-labile, sensitive to trypsin and insensitive to N-ethylmaleimide. With activated DNA as the preferred template/primer, the factor stimulates both the initial rate and the extent of DNA synthesis as a linear function of the concentration of the factor. The stimulation is abolished by aphidicol in but is unaffected by 2′, 3′ dideoxythymidine triphosphate.