Document Detail


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:  MEDLINE    
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; Research Support, Non-U.S. Gov't     Date:  2013-01-31
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  98     ISSN:  1945-7197     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-03-08     Completed Date:  2013-04-30     Revised Date:  2014-07-31    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1226-34     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Adult
Amidohydrolases / metabolism*
Arachidonic Acids / blood*
Cells, Cultured
Chorionic Gonadotropin, beta Subunit, Human / metabolism
Cilia / physiology
Embryo Implantation / physiology
Endocannabinoids / blood*
Ethanolamines / blood*
Fallopian Tubes / enzymology*,  physiopathology
Female
Humans
Luteal Phase / physiology
Oleic Acids / blood
Palmitic Acids / blood
Phospholipase D / metabolism
Polyunsaturated Alkamides / blood*
Pregnancy
Pregnancy, Ectopic / blood*,  physiopathology
Young Adult
Grant Support
ID/Acronym/Agency:
G0802524//Medical Research Council
Chemical
Reg. No./Substance:
0/Arachidonic Acids; 0/Chorionic Gonadotropin, beta Subunit, Human; 0/Endocannabinoids; 0/Ethanolamines; 0/N-acylethanolamines; 0/Oleic Acids; 0/Palmitic Acids; 0/Polyunsaturated Alkamides; 0/oleoylethanolamide; 544-31-0/palmidrol; 94421-68-8/anandamide; EC 3.1.4.4/Phospholipase D; EC 3.5.-/Amidohydrolases; EC 3.5.1.-/fatty-acid amide hydrolase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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