RESUMEN
Oligopeptide hormones are involved in cell-cell interaction during embryonal implantation and neuropeptide Y (NPY) is expressed in the human placenta and decidual cells in the third trimester of pregnancy. However, there is no report regarding the intrauterine localisation and the functions of NPY during the peri-implantation period. In the present study, the spatiotemporal changes in NPY expression in the murine uterus during the peri-implantation period were investigated using reverse transcription-polymerase chain reaction (RT-PCR), quantitative RT-PCR and immunohistochemical techniques, as were the effects of sex steroids on NPY mRNA expression in primary cultured murine uterine epithelial cells. Neuropeptide Y mRNA was increased in the pregnant murine uterus, as well as in the pseudopregnant murine uterus, during the peri-implantation period. Immunohistochemical analysis revealed increases in NPY expression in luminal and glandular epithelial cells and decidualised stromal cells. Neuropeptide Y mRNA expression was strongly induced in cultured epithelial cells in response to sex steroids. The data suggest that NPY is involved in cell-cell interactions during embryonic implantation.
Asunto(s)
Comunicación Celular , Implantación del Embrión , Endometrio/metabolismo , Neuropéptido Y/metabolismo , Animales , Comunicación Celular/efectos de los fármacos , Comunicación Celular/genética , Endometrio/química , Endometrio/efectos de los fármacos , Células Epiteliales/química , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Epitelio/química , Epitelio/efectos de los fármacos , Epitelio/metabolismo , Estradiol/farmacología , Femenino , Expresión Génica , Inmunohistoquímica , Ratones , Neuropéptido Y/análisis , Neuropéptido Y/genética , Embarazo , Progesterona/farmacología , ARN Mensajero/análisis , ARN Mensajero/metabolismoRESUMEN
Successful implantation involves a complex interaction between the endometrium and the embryo. It is well known that several neuropeptides are expressed in the endometrium and placenta during embryonal implantation, suggesting an important role as chemical mediators of the feto-maternal relationship. Ghrelin has recently been identified as the endogenous ligand for the GH secretagogue receptor. Ghrelin is a peptide hormone with many physiological functions, and its expression in the human placenta has been reported. To investigate the involvement of ghrelin in embryonal implantation, we assessed the spatio-temporal expression pattern of ghrelin and its receptor in the human endometrium and placenta through the normal menstrual cycle and in early pregnancy. We also examined the effect of ghrelin on the decidualization of endometrial stromal cells (ESC). Weak expression of ghrelin mRNA was detected in the nonpregnant endometrium, and it was dramatically increased in the decidualized endometrium. A GH secretagogue receptor mRNA was detected in the endometrium throughout the normal menstrual cycle and in early pregnancy, but not in the first trimester placenta. Immunohistochemical analysis using an antighrelin antibody revealed strong signals in decidual cells and extravillous trophoblast cells. Coculture with first trimester placenta up-regulated ghrelin mRNA expression by primary cultured ESC, although sex steroids and 8-bromo-cAMP had no effect. In addition, ghrelin enhanced the decidualization of ESC induced by 8-bromo-cAMP (8-Br-cAMP) in vitro. Thus, ghrelin is a novel paracrine/autocrine factor that is involved in cross-talk between the endometrium and embryo during embryonal implantation.