C1q is involved in human trophoblast invasion

During the development of human placenta, extravillous trophoblast (EVT) departs from anchoring chorionic villi and invades the maternal decidua. Immunohistochemical analysis of decidua obtained from voluntary abortions showed that C1q was widely distributed in the decidual stroma with intense staining around invading trophoblast, while undetectable in non pregnant uterus. Based on these findings, we hypothesized that C1q may be involved in the migration of EVT. To this end, we investigated the ability of EVT to adhere to solid-phase bound C1q and to migrate using a transwell model system with inserts coated with C1q. Our results showed that EVT strongly adhered to C1q to an extent similar to that observed for cell adhesion to fibronectin, a component of the extracellular matrix of decidua. Adhesion of EVT to C1q was inhibited by antibodies to gC1qR, which was detected on these cells by FACS analysis. Cells bound to C1q and to FN exhibited a markedly different morphological appearance. The cells attached to FN were spread out whereas those bound to C1q were much smaller with wide ruffles extending in multiple direction. EVT spread on FN contained a high number of actin-containing stress fibers as revealed by phalloidin staining as opposed to the peripheral distribution of actin in cells bound to C1q. C1q was also found to promote the migration of EVT, though to a lesser extent than FN. Interestingly, RT-PCR analysis showed that EVT expressed mRNA for the three chains of C1q. In conclusion, our results suggest that C1q is produced by EVT of maternal decidua and play a role in the migration and adhesion of these cells to the extracellular matrix of the decidua.