RhoA/MLC signaling pathway is involved in Δ⁹-tetrahydrocannabinol-impaired placental angiogenesis.
Cannabis is a widely used illicit drug and its abuse during pregnancy has been related to adverse reproductive outcomes. In addition, placental angiogenesis is considered to be responsible for the transport of nutrients critical for placental development and fetal growth. The purpose of this study is to determine the effects of Δ⁹-tetrahydrocannabinol (THC), the major component of cannabis, on placental angiogenesis, involving endothelial cell (EC) proliferation, migration and tube formation. Here, we observe dramatic alterations in placental vascular network of cannabis users correlated with an impaired HUVE cell proliferation, migration and tube formation after treated with THC. Mechanistically, the activity of RhoA/MLC is involved in the THC-impaired EC migration and angiogenesis. To further analyze the role of cannabis in mice placental and embryonic development, we inject pregnant mice with THC daily. This treatment results in an altered placental microvasculature, accompanied by the decreased expression of CD31 and activity of RhoA/MLC. Taken together, these findings identify THC plays a pivotal role in impairing placental angiogenesis potentially via RhoA/MLC signaling nexus.
['Chang|Xinwen|X|', 'Li|Hua|H|', 'Li|Yuhong|Y|', 'He|Qizhi|Q|', 'Yao|Julei|J|', 'Duan|Tao|T|', 'Wang|Kai|K|']
D000818:Animals D002465:Cell Movement D049109:Cell Proliferation D013759:Dronabinol D005260:Female D061307:Human Umbilical Vein Endothelial Cells D006801:Humans D008810:Mice, Inbred C57BL D055806:Microvessels D018994:Myosin Light Chains D018919:Neovascularization, Physiologic D010920:Placenta D011247:Pregnancy D015398:Signal Transduction D020742:rhoA GTP-Binding Protein
RhoA/MLC Placental angiogenesis Cannabis Δ⁹-Tetrahydrocannabinol Endothelial dysfunction