Leptin receptors are down-regulated in uterine implantation sites compared to interimplantation sites

Leptin is a circulating hormone that plays an important role in the regulation of metabolism, obesity, and reproduction. Leptin binds to its receptors on the cell membrane and is involved in the activation of STAT3. Recently, endometrium was suggested to be a novel target for leptin recently. We, therefore, examined the expression of leptin, leptin receptors, and STAT3 in the mouse uterus (implantation and interimplantation sites) to investigate the role of the leptin system during the early implantation period. Leptin mRNA was not detected in mouse uterine tissues or blastocysts, although adipose tissue, the positive control, showed a strong signal. Both of the receptor splice variants were expressed in the uterus and blastocysts, but the mRNA level was much lower in implantation sites compared to interimplantation sites. The mRNA expression of leptin receptors was determined to be higher in stromal cells than in the luminal epithelium using laser capture microdissection (LCM) analysis. Using immunohistochemistry, leptin was detected as a strong signal in the luminal epithelium and embryo, whereas the receptor was detected in subepithelial stromal cells rather than the luminal epithelium. As leptin itself was not detected by RT-PCR, the immunohistologically detected leptin may originate elsewhere, such as in adipose tissue. The differential expression of leptin receptors in implantation sites compared to interimplantation sites suggests that the leptin/leptin receptor system may be a delicate regulator of the implantation process.