Mol. Hum. Reprod. Advance Access originally published online on April 5, 2006
Molecular Human Reproduction 2006 12(5):321-333; doi:10.1093/molehr/gal036
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
9-Tetrahydrocannabinol inhibits cytotrophoblast cell proliferation and modulates gene transcription
1Clinical Division of Obstetrics & Gynaecology, Leicester Royal Infirmary, University Hospitals of Leicester NHS Trust and 2Reproductive Sciences Section, Department of Cancer Studies and Molecular Medicine, Leicester Medical School, University of Leicester, Leicester, UK
3 To whom correspondence should be addressed at: Reproductive Sciences Section, Department of Cancer Studies and Molecular Medicine, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary, P.O. Box 65, Leicester, Leicestershire, LE2 7LX, UK. E-mail: aht3{at}le.ac.uk
Cannabis use in pregnancy is associated with a range of obstetrical conditions. The molecular mechanisms underlying these effects have not been elucidated but are attributed to the actions of delta-9-tetrahydrocannabinol (
9-THC). In this study, concentrations of 9-THC equivalent to those found in the serum of cannabis users, i.e. 
20 µM, inhibited proliferation and activated a restricted tight transcriptional programme in the BeWo trophoblast cell line. Employing genome-wide expression profiling methods, we found that the pattern of gene expression differs from that described in the placenta of patients with fetal growth restriction (FGR), associated with either hypoxia or discordant dichorionic twins, or of patients with pre-eclampsia. It was also dissimilar to the patterns obtained from the transcriptome of other tissues, such as the mouse brain, treated with 9-THC. The expression of transcription factors, such as thyroid hormone receptor-ß1 (TRß1), and transcriptional co-repressors, such as histone deactylase 3 (HDAC3), was affected by 9-THC in a dose-dependent manner, whereby 15 µM 9-THC caused a 2.8-fold inhibition of TRß1 expression, but a 3.5-fold increase in HDAC3 expression. These data were confirmed by end-point RT–PCR analyses and underpin the observed 9-THC-induced inhibition of BeWo cell proliferation. Genes encoding for growth, apoptosis, cell morphology and ion exchange pathways were modulated by 15 µM 9-THC. This study may provide insight into the mechanisms underlying the effects of 9-THC and cannabis use upon placental development during pregnancy.
Key words: cannabis/cytotrophoblast/marijuana/microarray/tetrahydrocannabinol
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  B. P. F. Rutten and J. Mill Epigenetic Mediation of Environmental Influences in Major Psychotic Disorders Schizophr Bull, November 1, 2009; 35(6): 1045 - 1056. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. M. H. Habayeb, A. H. Taylor, S. C. Bell, D. J. Taylor, and J. C. Konje Expression of the Endocannabinoid System in Human First Trimester Placenta and Its Role in Trophoblast Proliferation Endocrinology, October 1, 2008; 149(10): 5052 - 5060. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A.H. Taylor, C. Ang, S.C. Bell, and J.C. Konje The role of the endocannabinoid system in gametogenesis, implantation and early pregnancy Hum. Reprod. Update, September 1, 2007; 13(5): 501 - 513. [Abstract] [Full Text] [PDF]
|
|