OR12-1 Leptin Is Transported across the Mouse Placenta

Abstract

The placenta is critical for mother-fetus physiological communication. It is particularly sensitive to changes in the nutritional and hormonal environments and can contribute to the programming of metabolic syndrome. Recent data, including from our laboratory, showed that the hormone leptin influences brain development during fetal life and mediates lifelong metabolic regulations. However, despite the documented capacity of the placenta in transporting various maternally-derived molecules, it is still unclear whether the placenta contributes to circulating fetal leptin. Here, we report that high levels of leptin receptor mRNA were detected in the mouse placenta during mid-gestation, particularly in trophoblast giant cells of the labyrinth zone, where mother-fetus exchanges take place. Remarkably, the main leptin receptor isoform expressed in the placenta was LepRa, which is critical for transporting leptin across cellular barriers. In addition, we found that leptin-deficient (ob/ob) embryos raised by heterozygous dams have significant levels of circulating leptin. Since the mouse placenta does not express leptin mRNA, this data support the idea that fetal leptin is maternally-derived. To further examine leptin transport from mother to fetus, fluorescently labeled bioactive leptin was injected through the tail vein of wild-type dams. Fluorescence was detected not only in the placenta but also in embryo including the hypothalamus, liver and pancreas as early as one minute after injection. In addition, maternally-injected leptin induces STAT3 activation in the placenta and various organs, including the CNS, of the embryo. We are currently examining whether this trans-placental leptin transport is altered in a context of maternal obesity. Taken together, our data provide direct evidence that maternal leptin is transported to the fetus across the mouse placenta.