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Elevated Anandamide and Related N-Acylethanolamine Levels Occur in the Peripheral Blood of Women With Ectopic Pregnancy and Are Mirrored by Changes in Peripheral Fatty Acid Amide Hydrolase Activity.
MedLine Citation:
PMID:  23372171     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Background:Studies from knockout mice suggest that perturbations in oviductal endocannabinoid levels, endocannabinoid receptors, or endocannabinoid degrading enzyme [fatty acid amide hydrolase (FAAH)] expression result in infertility secondary to physical trapping of embryos. Similar observations have been made in ectopic pregnant women together with a suggestion that the endocannabinoid receptor gene polymorphism 1359G/A (rs1049353) is associated with ectopic pregnancy. These observations led to the hypothesis that ectopic pregnancy is associated with a perturbation in levels of endocannabinoids and FAAH activity and that such changes are associated with impaired tubal function.Aims:The objective of the study was to quantify the plasma levels of endocannabinoids (anandamide, oleoylethanolamide, and palmitoylethanolamide) and evaluate blood endocannabinoid metabolizing enzyme activities FAAH and N-acyl-phosphatidyl-ethanolamine phospholipase D (NAPE-PLD) in ectopic pregnancy and normal pregnant controls and relate that to β-human chorionic gonadotropin (β-hCG) levels. Additionally, we wanted to examine the effect of endocannabinoids on cilia beat frequency in Fallopian tube epithelial cells ex vivo.Participants and Methods:Whole blood collected from ectopic and normal pregnancies was used for quantification of plasma endocannabinoid levels by ultra-HPLC-tandem mass spectrometry of FAAH and NAPE-PLD enzyme activities by radiometric assays, and β-hCG by immunoassay. Fallopian tube epithelial cells from healthy volunteers were treated with endocannabinoids and cilia beat frequency analyzed using a high-speed digital camera and CiliaFA software.Results:FAAH activity (P < .05) but not NAPE-PLD activity was significantly reduced in ectopic pregnancies. All 3 endocannabinoids levels were significantly higher (P < .05) in ectopic pregnancy. There was no correlation between endocannabinoids, enzyme activity, and β-hCG levels. Oleoylethanolamide (P < .05), but not methanandamide or palmitoylethanolamide, significantly decreased cilia beat frequency in Fallopian tube epithelial cells.Conclusion:Elevated endocannabinoid levels and reduced FAAH activity are associated with ectopic pregnancy and may modulate tubal function, suggesting dysfunctional endocannabinoid action in ectopic implantation. Oleoylethanolamide may play a critical role in embryo-tubal transport.
Authors:
Alpha K Gebeh; Jonathon M Willets; Monica Bari; Robert A Hirst; Timothy H Marczylo; Anthony H Taylor; Mauro Maccarrone; Justin C Konje
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-31
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  -     ISSN:  1945-7197     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-2-1     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Endocannabinoid Research Group (A.K.G., J.M.W., T.H.M., A.H.T., J.C.K.), Reproductive Sciences Section, Department of Cancer Studies and Molecular Medicine, and Department of Infection, Inflammation, and Immunity (R.A.H.), Leicester Royal Infirmary, University of Leicester, Leicester LE2 7LX, United Kingdom;J.C.K.), Department of Obstetrics and Gynaecology, University Hospitals of Leicester National Health Service Trust, Leicester Royal Infirmary, Leicester LE1 5WW, United Kingdom; Department of Experimental Medicine and Surgery (M.B.), University of Rome Tor Vergata, I-00133 Rome, Italy; and Center of Integrated Research (M.M.), Campus Bio-Medico University of Rome, I-00128 Rome, Italy; and European Center for Brain Research/Santa Lucia Foundation (M.M.), I-00143 Rome, Italy.
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