Localisation and function of the endocannabinoid system in the human ovary

Although anandamide (AEA) had been measured in human follicular fluid and is suggested to play a role in ovarian follicle and oocyte maturity, its exact source and role in the human ovary remains unclear. Immunohistochemical examination of normal human ovaries indicated that the endocannabinoid syst...

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Published in:	PloS one Vol. 4; no. 2; p. e4579
Main Authors:	El-Talatini, Mona R, Taylor, Anthony H, Elson, Janine C, Brown, Laurence, Davidson, Allan C, Konje, Justin C
Format:	Journal Article
Language:	English
Published:	United States Public Library of Science 24-02-2009 Public Library of Science (PLoS)
Subjects:	Analysis Anandamide Anatomy & physiology Arachidonic Acids - analysis Arachidonic Acids - physiology Cannabinoid CB2 receptors Cannabinoid Receptor Modulators - analysis Corpus luteum Embryo transfer Endocannabinoid system Endocannabinoids Enzymes Family medical history Fatty acids Fatty-acid amide hydrolase Female Fertilization Fluids Follicles Follicular Fluid Folliculogenesis Granulosa cells Granulosa Cells - chemistry Humans Hydrolase Immunohistochemistry Immunoreactivity In vitro fertilization Marijuana Maturation Medicine Medulla Medulla oblongata Menstruation Metabolism Molecular biology Obstetrics Oocytes Oocytes - cytology Oogenesis Ovarian cancer Ovarian Follicle - cytology Ovarian Follicle - growth & development Ovaries Ovary - chemistry Ovary - cytology Ovulation Pediatrics and Child Health Phospholipase Phospholipase D Phospholipases Physiology Polyunsaturated Alkamides - analysis Premature birth Proteins Receptors, Cannabinoid - analysis Reproductive system Studies Women's Health Womens health United Kingdom > UK
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Summary:	Although anandamide (AEA) had been measured in human follicular fluid and is suggested to play a role in ovarian follicle and oocyte maturity, its exact source and role in the human ovary remains unclear. Immunohistochemical examination of normal human ovaries indicated that the endocannabinoid system was present and widely expressed in the ovarian medulla and cortex with more intense cannabinoid receptor 2 (CB2) than CB1 immunoreactivity in the granulosa cells of primordial, primary, secondary, tertiary follicles, corpus luteum and corpus albicans. The enzymes, fatty acid amide hydrolase (FAAH) and N-acyclphosphatidylethanolamine-phospholipase D (NAPE-PLD), were only found in growing secondary and tertiary follicles and corpora lutea and albicantes. The follicular fluid (FF) AEA concentrations of 260 FF samples, taken from 37 infertile women undergoing controlled ovarian hyperstimulation for in vitro fertilisation and intracytoplasmic sperm injection with embryo transfer, were correlated with ovarian follicle size (P = 0.03). Significantly higher FF AEA concentrations were also observed in mature follicles (1.43+/-0.04 nM; mean+/-SEM) compared to immature follicles (1.26+/-0.06 nM), P = 0.0142 and from follicles containing morphologically assessed mature oocytes (1.56+/-0.11 nM) compared to that containing immature oocytes (0.99+/-0.09 nM), P = 0.0011. ROC analysis indicated that a FF AEA level of 1.09 nM could discriminate between mature and immature oocytes with 72.2% sensitivity and 77.14% specificity, whilst plasma AEA levels and FF AEA levels on oocyte retrieval day were not significantly different (P = 0.23). These data suggest that AEA is produced in the ovary, is under hormonal control and plays a role in folliculogenesis, preovulatory follicle maturation, oocyte maturity and ovulation.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Conceived and designed the experiments: MRET AHT ACD JCK. Performed the experiments: MRET AHT ACD. Analyzed the data: MRET AHT JCE LB. Contributed reagents/materials/analysis tools: AHT JCE LB ACD. Wrote the paper: MRET AHT LB JCK.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0004579