EFFECTS OF TUMOR-NECROSIS-FACTOR-ALPHA ON HUMAN TROPHOBLAST CELL-ADHESION AND MOTILITY

PROBLEM: Adhesive interaction between trophoblast cells and uterine en dometrial basement membrane is one of the critical processes in embryo implantation. This interaction is directly or indirectly regulated by hormones, growth factors, and cytokines. Since tumor necrosis factor- alpha (TNF-alpha) is synthesized by both decidual and trophoblast cell s, we hypothesized that TNF-alpha may play a regulatory role in tropho blast cell invasion. To test this hypothesis, we have used in vitro mo dels to determine the effect of TNF-alpha on human trophoblast cell ad hesion and motility, two major steps in trophoblast invasion. METHODS: The effect of TNF-alpha on the motility of extended-lifespan first tr imester trophoblasts (HTR) and JEG-3 choriocarcinoma cells was tested using the phagokinetic track motility assay. An in vitro adhesion assa y was used to determine the effect of TNF-alpha on the adhesion of HTR and JEG-3 cells to laminin, a major basement membrane component. In a ddition, the effect of TNF-alpha on the surface expression of the lami nin receptor beta 1 integrin subunit was examined using flow cytometry . RESULTS: HTR or JEG-3 cells were strongly adherent to laminin which was not significantly altered by TNF-alpha treatment. We also measured the effect of TNF-alpha on the surface expression of beta 1 integrin on HTR and JEG-3 cells; no difference was observed between control and treatment groups. Interestingly, the motility of both HTR and chorioc arcinoma JEG-9 cells was significantly inhibited by TNF-alpha. CONCLUS IONS: The role of TNF-alpha in human embryo implantation is currently unknown. Our data demonstrate that TNF-alpha does not alter trophoblas t cell adhesion to laminin, bur significantly inhibits trophoblast cel l motility in vitro, suggesting that TNF-alpha may play a regulatory r ole in trophoblast cell invasion.