Glycodelin-A Suppresses the Invasion of the Human Extravillous Cytotrophoblast.

The development of the placenta involves a series of complex, coordinated interactions between the fetal trophoblast cells and the maternal decidual cells. The invasion of the trophoblasts into the endometrium is crucial to placentation. The key cell in human placentation is the cytotrophoblast. After nidation, the cytotrophoblast differentiates into the villous cytotrophoblasts and the extravillous cytotrophoblasts (EVCTs). The invasive EVCTs appear as migratory cell columns invading through the endometrium. One of the invasive phenotypes of EVCTs is increased production of a set of extracellular matrix-degrading enzymes. Matrix metalloproteinases (MMP)-2 and MMP-9 are the most studied matrix-degrading enzymes in placental invasion and their proteinase activities are balanced by the tissue specific inhibitors of the MMPs (TIMP)-1 and TIMP-2. Glycodelin-A (GdA), a glycoprotein synthesized by the endometrial glands but not the trophoblast, is upregulated during first trimester which coincides with the time of trophoblast invasion. We hypothesize that glycodelin-A is a paracrine regulator generated by the deciduas that fine-tune the invasion process of human trophoblast. Trans-well invasion assay was used to examine the effect of GdA on the invasiveness of the immortalized first trimester extravillous cytotrophoblast (TEV-1) cell line. MMP2/MMP9 and TIMP1/TIMP2 secretions and activities were determined by ELISA and gelatin zymographic analysis respectively. Our results show that GdA significantly reduced the invasiveness and MMP2 secretion while increased the activities of TIMP-1 and TIMP-2 of TEV-1. No significant effect on MMP9 secretion was observed. Taken together, GdA may produce an inhibitory effect on trophoblast invasion by regulating the MMP pathways. Further works are required to characterize the biological role of GdA in trophoblast invasion.