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The Leptin System during Human Endometrial Receptivity and Preimplantation Development

Instituto Valenciano de Infertilidad Foundation (A.C., J.A.H., J.M., A.P., C.S.) and Department of Pediatrics (A.C., A.P., C.S.), Obstetrics and Gynaecology, School of Medicine, University of Valencia, 46010 Valencia, Spain

Address all correspondence and requests for reprints to: Carlos Simón, Instituto Valenciano de Infertilidad, Plaza Policía Local 3, 46015 Valencia, Spain. E-mail: csimon{at}interbook.net.

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 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.

This work was supported by Fondo de Investigaciones Sanitarias Grant FISS 02/1169 and Sociedad Española de Fertilidad (2001 Research Grant). A.C. is a predoctoral fellow financed by Programa para la Formación de Personal Universitario from the Ministerio de Educación, Cultura y Deporte (Madrid, Spain) of the Spanish Government.

Results from this work were presented in part at the 50th Annual Meeting of the Society for Gynecologic Investigation, Washington, DC, March 2003.

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.

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