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Leptin and Leptin Receptor Are Expressed in the Human Endometrium and Endometrial Leptin Secretion Is Regulated by the Human Blastocyst¹

Instituto de Investigaciones Materno Infantil, Facultad de Medicina (R.R.G., L.D.), Hospital San Borja Arriarán, Universidad de Chile, Santiago de Chile, Chile; and Fundación del Instituto Valenciano de Infertilidad para el estudio de la Reproducción (FIVIER) and Departamento de Pediatría, Obstetría y Ginecología (P.C.-C., M.J., A.M., A.P., C.S.), Universidad de Valencia, 46020 Valencia, Spain.

Address correspondence and requests for reprints to: Carlos Simón, Instituto Valenciano de Infertilidad, Guardia Civil 23, 46020 Valencia, Spain. E-mail: csimon{at}interbook.net

Embryonic implantation is a crucial event for the human reproductive function. Cytokines and paracrine molecules have been proposed as putative local regulators of this process. The leptin or the OB protein has been linked to the reproductive function and inflammatory response. In the present study, we describe for the first time the expression of leptin and leptin receptor (long form) in the secretory endometrium and that endometrial leptin secretion is regulated in vitro by the human blastocyst. Leptin and leptin receptor messenger RNA and protein were identified in secretory endometrium and in cultured endometrial epithelial cells (EECs) by RT-PCR, Western blot, and immunohistochemistry. The concentrations of immunoreactive leptin secreted by human embryos alone or cocultured with EECs were also assessed. We found that human blastocysts secrete significantly higher levels of leptin than arrested embryos. In contrast, leptin concentrations secreted by arrested embryos cocultured with EECs were significantly higher than blastocysts cocultured with EECs. These findings suggest that the human endometrium is a site for local production and a target tissue for circulating leptin. Expression of leptin and its functional receptor in the endometrium and regulation of endometrial leptin secretion by the human embryo suggests that the leptin system may be implicated in the human implantation process.

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