The Leptin System during Human Endometrial Receptivity and Preimplantation Development
Journal of Clinical Endocrinology and Metabolism
The leptin system is implicated in the regulation of body weight and reproductive function, acting at endocrine and paracrine levels. This ligand-receptor system is mandatory for embryonic implantation in rodents. Here, we investigate the expression pattern of total leptin receptor (OB-R T ), the long form (OB-R L ) and short isoforms HuB219.1 and HuB219.3 in the human endometrium. Furthermore, we studied leptin and OB-R T mRNA during human embryonic preimplantation development and the
... nt and the embryonic regulation of the endometrial OB-R L . Leptin receptor expression and its isoforms increase in the luteal phase and peak in the late part. Leptin receptor was localized at the epithelial and glandular epithelium using in situ hybridization. Reverse transcription-nested PCR showed the presence of OB-R T mRNA at all the embryonic stages, whereas leptin mRNA was only detected at the blastocyst stage. The embryonic regulation of endometrial epithelial OB-R L and HuB219.3 was studied, and no impact was found. Finally, OB-R L was immunohistochemically localized in the human cytotrophoblast and maternal decidua. These findings suggest that secretory endometrium is a target tissue for leptin action, and oocytes and preimplantation embryos possess OB-R mRNA, indicating that leptin may be necessary for embryonic development. Furthermore, leptin mRNA is specifically expressed at the blastocysts stage, suggesting a function in the blastocyst-endometrial dialogue. (J Clin Endocrinol Metab 89: 2442-2451, 2004) Abbreviations: DEPC, Diethylpyrocarbonate; dNTP, deoxynucleotide triphosphate; EEC, endometrial epithelial cells; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; IVF, in vitro fertilization; OB-R, leptin receptor; OB-R L , long-form leptin receptor; OB-R T , total leptin receptor; QF-PCR, quantitative fluorescent PCR; RT, reverse transcription; SSC, saline sodium citrate; STAT3, signal transducer and activator of transcription-3. JCEM is published monthly by The Endocrine Society (http://www. endo-society.org), the foremost professional society serving the endocrine community. FIG. 7. General hypothesis of the human leptin system interactions at the maternal-embryonic interphase during the preimplantation and implantation phases. During the preimplantation phase, the embryo possesses the leptin receptor, which can be activated through the endocrine and endometrial leptin, thereby promoting the embryonic metabolism. When the embryo reaches the blastocyst stage, leptin is expressed, and this molecule may activate the leptin receptor, which peaks in the receptive endometrium, thereby facilitating the embryo implantation process.