Mol. Hum. Reprod. Advance Access published online on April 5, 2006
Molecular Human Reproduction, doi:10.1093/molehr/gal036
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1 Clinical Division of Obstetrics & Gynaecology, Leicester Royal Infirmary, University Hospitals of Leicester NHS Trust, University
of Leicester, Leicester, UK
* To whom correspondence should be addressed. 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 (
Received May 25, 2005
Revised December 15, 2005
Accepted March 1, 2006
Article
Manjiri Khare 1,
Anthony H. Taylor 2 *,
Justin C. Konje 2,
and
Stephen C. Bell 2
9-Tetrahydrocannabinol inhibits cytotrophoblast cell proliferation and modulates gene transcription
2 Clinical Division of Obstetrics & Gynaecology, Leicester Royal Infirmary, University Hospitals of Leicester NHS Trust; Reproductive Sciences Section, Department of Cancer Studies and Molecular Medicine, Leicester Medical School, University of Leicester, Leicester, UK
Anthony H. Taylor, E-mail: aht3{at}le.ac.uk
Abstract 
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-
1 (TR1), 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 TR1 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.
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