Leptin modulates extracellular matrix molecules and metalloproteinases: possible implications for trophoblast invasion

Leptin is a circulating hormone which plays an important role in the regula tion of energy balance, haemopoiesis and reproduction. Leptin and its recep tor (leptin-R) are localized in human placental tissue but their function i s not known. In this study we have investigated the expression of leptin an d leptin-R in the human placenta with particular attention to extravillous cytotrophoblastic cell islands and cell columns which play a pivotal role i n trophoblast invasion and placental growth. We demonstrate that leptin-R i mmunoreactivity shows a strong expression in the distal extravillous cytotr ophoblastic cells of cell columns invading the basal plate, whereas leptin expression is homogeneously expressed in all the cellular components of cel l columns. Since the invasive ability of the distally located extravillous cytotrophoblast of cell columns is known to be regulated by a variety of pr oteases and some extracellular matrix molecules, we tested the influence of leptin on the in-vitro production of matrix metalloproteinase (MMP)-2, MMP -9 and fetal fibronectin (fFN) by cytotrophoblastic cells. We demonstrate t hat leptin increases, in a dose-dependent manner, the secretion of immunore active MMP-2 and fFN and enhances the activity of MMP-9 in cultured cytotro phoblastic cells. Our results suggest that leptin and leptin-R could have a role in the invasive processes of the extravillous cytotrophoblastic cells by modulating the expression of MMPs. In addition, these results provide a foundation for studying pathological conditions characterized by insuffici ent or excessive trophoblast.