The endocannabinoid 2-arachidonoylglycerol (2-AG) and metabolizing enzymes during rat fetoplacental development: a role in uterine remodelling.
The main endocannabinoids (EC) identified in mammalian tissues are N-arachidonoylethanolamide (AEA, anandamide), and 2-arachidonoylglycerol (2-AG). AEA levels are critical in pregnancy, especially during implantation, decidualization, and placental development. As 2-AG functions in pregnancy are still largely undefined, we hypothesized that it may also have a role during fetoplacental development. We showed that 2-AG is not only present in the rat mesometrial decidua and plasma during fetoplacental development, but that both 2-AG synthesizing (diacylglycerol lipase) and degradation (monoacylglycerol lipase) enzymes are expressed by decidual cells. While lower concentrations of 2-AG induced apoptosis of rat primary decidual cells, via the CB1 receptor, higher concentrations induced a dramatic effect on cell morphology, cell viability and lactate dehydrogenase release, triggered through a mechanism independent of CB1. This study provides evidences that 2-AG fluctuation in maternal tissues throughout normal pregnancy is primarily regulated by its metabolizing enzymes. Together, these data supports the hypothesis that a deregulation of the endocannabinoid system through aberrant cannabinoid signalling may impact normal uterine remodelling process and consequently normal pregnancy.
Fonseca
B M
BM
Departamento de Bioquímica, Faculdade de Farmácia da Universidade do Porto, Porto, Portugal.
Correia-da-Silva
G
G
Taylor
A H
AH
Lam
P M W
PM
Marczylo
T H
TH
Bell
S C
SC
Konje
J C
JC
Teixeira
N A
NA
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D001095:Arachidonic Acids / Q000378:metabolism*; D015153:Blotting, Western; D002470:Cell Survival; D002478:Cells, Cultured; D003656:Decidua / Q000166:cytology / Q000378:metabolism; D063388:Endocannabinoids; D005260:Female; D005989:Glycerides / Q000378:metabolism*; D007150:Immunohistochemistry; D008071:Lipoprotein Lipase / Q000235:genetics / Q000378:metabolism; D008297:Male; D008994:Monoacylglycerol Lipases / Q000235:genetics / Q000378:metabolism; D010929:Placentation / Q000235:genetics / Q000502:physiology*; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D014599:Uterus / Q000378:metabolism*
D001095:Arachidonic Acids; D063388:Endocannabinoids; D005989:Glycerides; C094503:glyceryl 2-arachidonate; D008994:Monoacylglycerol Lipases; D008071:Lipoprotein Lipase