Molecular Human Reproduction, Vol. 6, No. 10, 951-958,
October 2000
© 2000 European Society of Human Reproduction and Embryology
Pregnancy |
Leptin modulates extracellular matrix molecules and metalloproteinases: possible implications for trophoblast invasion
1 Institute of Normal Human Morphology, 2 Institute of Clinical Medicine, Faculty of Medicine, University of Ancona, Ancona, Italy, 3 Department of Obstetrics and Gynaecology, University of Geneva, Geneve, Switzerland
Abstract
Leptin is a circulating hormone which plays an important role in the regulation of energy balance, haemopoiesis and reproduction. Leptin and its receptor (leptin-R) are localized in human placental tissue but their function is not known. In this study we have investigated the expression of leptin and leptin-R in the human placenta with particular attention to extravillous cytotrophoblastic cell islands and cell columns which play a pivotal role in trophoblast invasion and placental growth. We demonstrate that leptin-R immunoreactivity shows a strong expression in the distal extravillous cytotrophoblastic cells of cell columns invading the basal plate, whereas leptin expression is homogeneously expressed in all the cellular components of cell columns. Since the invasive ability of the distally located extravillous cytotrophoblast of cell columns is known to be regulated by a variety of proteases 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 that leptin increases, in a dose-dependent manner, the secretion of immunoreactive MMP-2 and fFN and enhances the activity of MMP-9 in cultured cytotrophoblastic 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 insufficient or excessive trophoblast invasion.
fibronectin/leptin/leptin-R/metalloproteases/placenta
Notes
4 To whom correspondence should be addressed at: Institute of Normal Human Morphology–Anatomy, University of Ancona, Via Tronto, 10/a, I-60020 Ancona, Italy. E-mail: m.castellucci{at}popcsi.unian.it
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