GLYCOSYLATION OF HUMAN TROPHOBLAST INTEGRINS IS STAGE AND CELL-TYPE-SPECIFIC

Cytotrophoblasts are the specialized epithelial cells of the placenta. During the first trimester, a subpopulation of chorionic villus cytot rophoblasts differentiates along an invasive pathway and penetrates th e maternal endometrium, decidua and spiral arterioles. Cytotrophoblast invasiveness declines rapidly during the second half of gestation. Is olated cytotrophoblasts of different gestational ages retain this diff erential invasiveness in culture. To determine whether the properties of integrin receptors for extracellular matrix molecules differ betwee n invasive and non-invasive cytotrophoblasts, detergent extracts of is olated cytotrophoblasts of different gestational ages, and of first-tr imester villous fibroblasts, were immunoprecipitated with subunit-spec ific anti-beta 1 integrin antibodies. Striking alterations in electrop horetic mobility were observed in beta 1 integrins from first-trimeste r cytotrophoblasts, as compared with those from term cytotrophoblasts or first-trimester villous fibroblasts, suggesting a cell-type-specifi c, temporally regulated alteration in glycosylation. Treatment of tota l first-trimester cytotrophoblast beta 1 integrins or the isolated alp ha 5/beta 1 fibronectin receptor with endo-beta-galactosidase restored electrophoretic mobility to control levels, suggesting the presence o f polylactosamine-bearing oligosaccharides. Further analysis by enzyme digestion and lectin-affinity chromatography suggested that they cons isted of at least three antennae and short, sialylated lactosamine uni ts. These oligosaccharides did not affect the affinity of the first-tr imester cytotrophoblast fibronectin receptor for fibronectin. However, this receptor bound more strongly to wheat germ agglutinin than contr ol fibronectin receptor and resisted elution by high concentrations of sugar hapten, requiring ionic detergent for removal. These results su ggested that the altered glycosylation affected the conformation of th e fibronectin receptor.