Silencing or amplification of endocannabinoid signaling in blastocysts via CB1 compromises trophoblast cell migration

J Biol Chem. 2012 Sep 14;287(38):32288-97. doi: 10.1074/jbc.M112.381145. Epub 2012 Jul 24.


Endocannabinoid signaling plays key roles in multiple female reproductive events. Previous studies have shown an interesting phenomenon, that mice with either silenced or elevated endocannabinoid signaling via Cnr1 encoding CB(1) show similar defects in several pregnancy events, including preimplantation embryo development. To unravel the downstream signaling of this phenomenon, microarray studies were performed using RNAs collected from WT, Cnr1(-/-), and Faah(-/-) mouse blastocysts on day 4 of pregnancy. The results indicate that about 100 genes show unidirectional changes under either silenced or elevated anandamide signaling via CB(1). Functional enrichment analysis of the microarray data predicted that multiple biological functions and pathways are affected under aberrant endocannabinoid signaling. Among them, genes enriched in cell migration are suppressed in Cnr1(-/-) or Faah(-/-) blastocysts. Cell migration assays validated the prediction of functional enrichment analysis that cell mobility and spreading of either Cnr1(-/-) or Faah(-/-) trophoblast stem cells are compromised. Either silenced or elevated endocannabinoid signaling via CB(1) causes similar changes in downstream targets in preimplantation embryos and trophoblast stem cells. This study provides evidence that a tightly regulated endocannabinoid signaling is critical to normal preimplantation embryo development and migration of trophoblast stem cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blastocyst / cytology
  • Cell Movement
  • Embryo Implantation
  • Endocannabinoids / metabolism*
  • Female
  • Gene Silencing*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Oligonucleotide Array Sequence Analysis
  • Receptor, Cannabinoid, CB1 / metabolism*
  • Signal Transduction
  • Stem Cells / cytology
  • Trophoblasts / metabolism*
  • Wound Healing


  • Endocannabinoids
  • Receptor, Cannabinoid, CB1