2-Arachidonoylglycerol impairs human cytotrophoblast cells syncytialization: influence of endocannabinoid signalling in placental development

Mol Cell Endocrinol. 2015 Jan 5:399:386-94. doi: 10.1016/j.mce.2014.09.005. Epub 2014 Sep 6.

Abstract

A balanced cytotrophoblast cell turnover is crucial for placental development and anomalies in this process associated with gestational diseases. The endocannabinoid system (ECS) has emerged as a new player in several biological processes. However, its influence during placental development is still unknown. We report here the expression of the endocannabinoid 2-arachidonoylglycerol (2-AG) main metabolic enzymes in human cytotrophoblasts and syncytiotrophoblast. We also showed that 2-AG induced a decrease in placental alkaline phosphatase activity, human chorionic gonadotropin secretion and Leptin mRNA levels. Moreover, 2-AG reduced glial cell missing 1 and syncytin-2 transcription and the number of nuclei in syncytium. These effects were mediated by cannabinoid receptors and may result from 2-AG inhibition of the cAMP/PKA signalling pathway. Our data suggest that 2-AG may interfere with the biochemical and morphological differentiation of human cytotrophoblasts, through a CB receptor-dependent mechanism, shedding light on a role for the ECS in placental development.

Keywords: 2-arachinoylglycerol; Endocannabinoid signalling; Human cytotrophoblasts; Placenta; Syncytialization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alkaline Phosphatase / metabolism
  • Arachidonic Acids / metabolism*
  • Chorionic Gonadotropin / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Endocannabinoids / metabolism*
  • Female
  • Giant Cells / cytology
  • Giant Cells / metabolism*
  • Glycerides / metabolism*
  • Humans
  • Leptin / metabolism
  • Pregnancy
  • Pregnancy Proteins / metabolism
  • Signal Transduction / physiology*
  • Trophoblasts / cytology
  • Trophoblasts / metabolism*

Substances

  • Arachidonic Acids
  • Chorionic Gonadotropin
  • ERVFRD-1 protein, human
  • Endocannabinoids
  • Glycerides
  • Leptin
  • Pregnancy Proteins
  • glyceryl 2-arachidonate
  • Cyclic AMP-Dependent Protein Kinases
  • Alkaline Phosphatase