Effects of Δ(9)-tetrahydrocannabinol (THC) on human amniotic epithelial cell proliferation and migration
Authors: K Wang
J T Wu
J L Yao
X W Chang
Q Z He
M Liu
T Duan
Journal: Toxicology (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: MMPs; amniotic epithelial cell; cannabinoid receptor type 1 (CB1); migration; proliferation
Affiliations: Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200040, PR China., Department of Pathology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200040, PR China., Department of Obstetrics, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200040, PR China., Department of Obstetrics, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200040, PR China. Electronic address: ., Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200040, PR China. Electronic address: .

Abstract:  Background: The deleterious effects of cannabis consumption for fertility and pregnancy outcome are recognized for years. The main psychoactive molecule of cannabis, Δ(9)-tetrahydrocannabinol (THC) is able to cross the placenta barrier and cause alterations in fetal growth, low birth weight and preterm labor. However, the effects of THC on the human placenta amnion are still unknown. Methods: The distributions of CB1R and CB2R in human amnion tissues were observed by immunohistochemistry (IHC). Human amniotic epithelial cell proliferation and migration in response to THC treatment were measured by MTS and transwell assays, respectively. The PCR array was performed to study the key regulators involved in the cell migration. The protein levels of CB1R, CB2R in amnion tissues and MMP2, MMP9 in cells were detected by western blotting. Small interfering RNAs (siRNAs) were used to knockdown MMP2 and MMP9 in WISH cells. Results: Our results indicated that both CB1R and CB2R primarily identified in the epithelial layer of human placental amnion tissue. The CB1R expression in the amnion tissue was higher in the preterm group than normal control. High-dose of THC (30uM, but not 20 and 10uM) significantly inhibited (p&lt;0.01) human amniotic epithelial cell lines (WISH) proliferation. Meanwhile, THC at both 10uM and 20uM (p&lt;0.05) significantly suppressed cells migration in both WISH and primary human amniotic epithelial cells. The PCR array data and siRNA experiments demonstrated that MMP2/9 were tightly involved in the regulation of THC-inhibited cell migration in WISH cells. Conclusion: These results suggested that THC inhibited the migration of human amniotic epithelial cell through the regulation of MMP2 and MMP9, which in turn altered the development of the amnion during the gestation and partially resulted in preterm labor and other adverse pregnancy outcomes. 

Retracted: No

PubPeer comments:
 This paper states*  To explore the role of THC in human amniotic epithelial cells, cell proliferation and migration were conducted using human amniotic epithelial (WISH) cell line, originally purchased from the Type Culture Collection of the Chinese Academy of Sciences, Shanghai, China. The WISH cell, an immortalized cell line, is widely used as an amniotic epithelial cell model for studying normal amniotic epithelium function * But as it is known since 1968 and confirmed in the 1980 s this is a HeLa contaminated cell line. This fact is well know and the WISH cell line is indicated in all cell collections as being not of amniotic origin. Thus the conclusions derived in this paper from experiments carried out on the WISH cell line are invalid. See the relevant [Cellosaurus entry] ,