Differential regulation of endocannabinoid synthesis and degradation in the uterus during embryo implantation.

Differential regulation of endocannabinoid synthesis and degradation in the uterus during embryo implantation. Research Abstract Details 

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Differential regulation of endocannabinoid synthesis and degradation in the uterus during embryo implantation. Abstract Text:

Haibin Wang,Huirong Xie,Xiaofei Sun,Philip J Kingsley,Lawrence J Marnett,Benjamin F Cravatt,Sudhansu K Dey,

Preimplantation embryo development to the blastocyst stage and uterine differentiation to the receptive state are prerequisites for embryo implantation. Burgeoning evidence suggests that endocannabinoid signaling is critical to early pregnancy events. Anandamide (N-arachidonoylethanolamine) and 2-AG (2-arachidonoylglycerol) are two major endocannabinoids that bind to and activate G-protein coupled cannabinoid receptors CB1 and CB2. We have previously shown that a physiological tone of anandamide is critical to preimplantation events in mice, since either silencing or amplification of anandamide signaling causes retarded development and oviductal retention of embryos via CB1, leading to deferred implantation and compromised pregnancy outcome. Whether 2-AG, which also influences many biological functions, has any effects on early pregnancy remains unknown. Furthermore, mechanisms by which differential uterine endocannabinoid gradients are established under changing pregnancy state is not clearly understood. We show here that 2-AG is present at levels one order of magnitude higher than those of anandamide in the mouse uterus, but with similar patterns as anandamide, i.e. lower levels at implantation sites and higher at interimplantation sites. We also provide evidence that region- and stage-specific uterine expression of N-acylphosphatidylethanolamine-specific phospholipase D (NAPE-PLD) and fatty acid amide hydrolase (FAAH), and sn-1-diacylglycerol (DAG) lipase alpha (DAGLalpha) and monoacylglycerol lipase (MAGL) for synthesis and hydrolysis of anandamide and 2-AG, respectively, creates endocannabinoid gradients conducive to implantation. Our genetic evidence suggests that FAAH is the major degrading enzyme for anandamide, whereas COX-2, MAGL and to some extent COX-1 participate in metabolizing 2-AG in the pregnant uterus. The results suggest that aberrant functioning of these pathways impacting uterine anandamide and/or 2-AG levels would compromise pregnancy outcome.

Differential regulation of endocannabinoid synthesis and degradation in the uterus during embryo implantation. Publishing Authors By Initials

H Wang,H Xie,X Sun,PJ Kingsley,LJ Marnett,BF Cravatt,SK Dey,

For similar urogenital system: genitalia: genitalia, female: uterus research abstracts see: urogenital system: genitalia: genitalia, female: uterus research

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Differential regulation of endocannabinoid synthesis and degradation in the uterus during embryo implantation. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Prostaglandins & other lipid mediators

VOLUME: 83

Page Numbers: 62-74

Journal Abbreviation: Prostaglandins Other Lipid Med

ISSN: 1098-8823

DAY: 28

MONTH: 11

YEAR: 2006

Differential regulation of endocannabinoid synthesis and degradation in the uterus during embryo implantation. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9808648

Differential regulation of endocannabinoid synthesis and degradation in the uterus during embryo implantation. Keywords Mesh Terms:

KEYWORDS: Uterus

MESH TERMS: metabolism

Chemical & Substance for Abstract: Differential regulation of endocannabinoid synthesis and degradation in the uterus during embryo implantation. Information

Substance Name: fatty-acid amide hydrolase

Registry Number: EC 3.5.1.-

Grant and Affiliation Information for Differential regulation of endocannabinoid synthesis and degradation in the uterus during embryo implantation.

AFFILIATION: Department of Pediatrics, Division of Reproductive and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.

Country: United States

AGENCY: United States NICHD

GRANT: R37 HD012304-27

ACRONYM: HD

MEDLINETA: Prostaglandins Other Lipid Med

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