Role of GnRH-GnRH receptor signaling at the maternal-fetal interface

Abstract

Objective: To investigate the expression and function of GnRH and GnRH receptor (GnRHR) subtypes at the maternal-fetal interface. Design: In vitro experiments using freshly isolated human trophoblast cells, decidual stromal cells (DSCs), and immortalized cell lines. Setting: University teaching hospital. Patient(S): Placenta-fetal membranes from term deliveries. Intervention(s): Human trophoblast and DSCs were isolated, purified, and cultured. Main Outcome Measure(s): Expression of GnRH-I, GnRH-II, and GnRHR-I mRNA and protein in human trophoblast cell lines and tissues were evaluated by reverse-transcription polymerase chain reaction and Western blot. The effect of GnRH-I and -II on the production of select cytokines (hCG, interleukin [IL] 8, IL-6, matrix metalloproteinase 3, monocyte chemoattractant protein 1, vascular endothelial growth factor, soluble Fms-like tyrosine kinase 1, urokinase-type plasminogen activator, and plasminogen activator inhibitor 1) were measured by ELISA and normalized for protein content. Result(s): GnRH-I, GnRH-II, and GnRHR-I mRNA and protein were identified in trophoblasts and decidua. GnRH-I and -II stimulated hCG production by trophoblast and trophoblast-derived cell lines in a dose-dependent fashion (e. g., 2.8-fold, from 2.5 +/- 0.5 to 7.0 +/- 0.4 ng/mg protein per 24 h, for 1,000 nmol/L GnRH-I and 2.4-fold, from 2.5 +/- 0.5 to 6.1 +/- 0.6 ng/mg protein per 24 h, for 1,000 nmol/L GnRH-II) without affecting the production of other cytokines. Conclusion(s): Trophoblasts and decidua express GnRH-I, GnRH-II, and GnRHR-I mRNA and protein. GnRH-I and -II selectively stimulate hCG production by trophoblast cells without altering the production of select cytokines by trophoblasts or decidua. The role of GnRH-GnRHR signaling at the maternal-fetal interface therefore appears to be limited to the regulation of trophoblast hCG production. (Fertil Steril (R) 2010;94:2680-7. (C) 2010 by American Society for Reproductive Medicine.)