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

Fertil Steril. 2010 Dec;94(7):2680-7. doi: 10.1016/j.fertnstert.2010.03.016. Epub 2010 Apr 18.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Chlorocebus aethiops
  • Chorionic Gonadotropin / genetics
  • Chorionic Gonadotropin / metabolism
  • Extraembryonic Membranes / metabolism
  • Extraembryonic Membranes / physiology
  • Female
  • Gonadotropin-Releasing Hormone / genetics
  • Gonadotropin-Releasing Hormone / metabolism
  • Gonadotropin-Releasing Hormone / physiology*
  • Humans
  • Maternal-Fetal Relations / physiology*
  • Mice
  • Placenta / metabolism
  • Placenta / physiology
  • Pregnancy
  • Pregnancy Trimester, First / genetics
  • Pregnancy Trimester, First / metabolism
  • Pregnancy Trimester, First / physiology
  • Receptors, LHRH / genetics
  • Receptors, LHRH / metabolism
  • Receptors, LHRH / physiology*
  • Signal Transduction / physiology
  • Trophoblasts / metabolism
  • Trophoblasts / physiology

Substances

  • Chorionic Gonadotropin
  • Receptors, LHRH
  • Gonadotropin-Releasing Hormone