Effects of leptin and its Mechanisms of Action on Mammalian Trophoblast Cells

Trustees Of Boston University, Boston

Investigators

Abstract

Central to an understanding of successful pregnancies is determining how the placenta attaches itself to the uterine wall of the mother. The outer lining of the placenta contains a layer of cells (trophoblasts), which have the property of being able to invade the uterine lining, thus establishing the placenta. How the invasion process is initiated and regulated is uncertain. In this project, the hypothesis that the reproductive hormone leptin stimulates invasiveness of trophoblast cells will be investigated in trophoblast cells grown on an artificial, protein-coated membrane. Invasive cells secrete enzymes that degrade the protein coating, and permit the cells to move through tiny pores in the membrane; the number of cells penetrating the membrane are counted under a microscope. The ability of leptin to stimulate invasion of trophoblasts from placentas at early and late gestation will be examined; we predict that leptin will promote invasion only in trophoblasts from early-stage placentas. The molecular mechanisms by which leptin stimulates invasiveness will be determined by examining changes in intracellular signaling molecules and gene expression induced by leptin. Placentas will be studied in species representing the two most abundant mammalian orders. The mouse placenta does not produce leptin, but expresses receptors for leptin and is therefore sensitive to leptin actions. The little brown bat placenta produces and secretes leptin (as does the human placenta), and like the mouse placenta is a target for leptin. The effects of leptin on mouse and bat placental function will be compared. Broader impacts of this project include: 1) documentation of the importance of leptin in establishing the placenta in diverse mammals; 2) understanding the role of leptin as a general signal for cell migration and invasion (i.e., in other cell types where leptin is known to act and where cells are invasive); 3) understanding gestational stage-dependent actions of hormones on trophoblast cells; and 4) education of young scientists-in-training and outreach to include participation of underrepresented minorities (one postdoctoral fellow, one to two graduate students and four undergraduates students will be mentored per year on this project).