Tuning the oviduct to the anandamide tone

Schuel, Herbert

doi:10.1172/jci29424

Cited by 43 publications

(38 citation statements)

References 14 publications

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“…These results support our speculation that changes in AEA levels during the estrous cycle might regulate fertilization-competent sperm release from oviductal reservoirs, thus allowing their ascent to the fertilization site. Based on our results and previous reports (Schuel 2006), we propose that an AEA gradient created during the peri-ovulatory period might be one of the signals that participate in the fertilization process promoting sperm capacitation and/or hyperactivation thus enhancing the ability of sperm to be release from oviductal reservoirs. Another possibility is that AEA, as a second messenger, might mediate the effect of other molecules, such as sulfated glycoconjugates, in the oviductal fluid and be involved in sperm releasing signaling pathways at the time of fertilization.…”

Section: Discussionsupporting

confidence: 77%

“…Since our results indicated that SPZ and the oviductal epithelium expressed CB-R and FAAH and previous results suggested that an oviductal AEA gradient could be modulating sperm functions (Maccarrone et al 2005, Schuel 2006), the next step was to investigate whether AEA participates in sperm-oviduct interaction. We therefore co-incubated BOEC with 0.5!10 6 SPZ/ml and nanomolar concentrations of CB-R agonists because at mid-cycle AEA is present in human oviductal fluid at nanomolar concentrations (Schuel et al 2002b) and because it was the lowest agonist concentration that had an effect (see Materials and Methods).…”

Section: Experiments 1 (Co-incubations)mentioning

confidence: 71%

“…Some studies suggest the existence of an AEA concentration gradient in the oviduct (Schuel 2006). Wang et al (2006) have demonstrated in mice that a critical balance between AEA synthesis and degradation creates locally an appropriate 'anandamide tone' required for normal embryo development, oviductal transport, implantation, and pregnancy.…”

Section: Discussionmentioning

confidence: 99%

“…AEA is synthesized from membrane phospholipid precursors by N-acylphosphatidylethanolamine-selective phospholipase D. Once released, AEA effect is quickly terminated by membrane-bound fatty acid amide hydrolase (FAAH; Di Marzo et al 1994), suggesting a critical role for this lipid during cell signaling (Schuel 2006). CB-R are widely distributed in neuronal cells and in somatic cells from peripheral organs including the reproductive system (Paria et al 2002, Wang et al 2004, Maccarrone et al 2005, Schuel & Burkman 2005.…”

Section: Introductionmentioning

confidence: 99%

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The endocannabinoid system in bull sperm and bovine oviductal epithelium: role of anandamide in sperm–oviduct interaction

Gervasi¹,

Rapanelli²,

Ribeiro³

et al. 2009

Reproduction

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Anandamide binds to cannabinoid receptors and plays several central and peripheral functions. The aim of this work was to study the possible role for this endocannabinoid in controlling sperm-oviduct interaction in mammals. We observed that bull sperm and bovine oviductal epithelial cells express cannabinoid receptors, CB1 and CB2, and fatty acid amide hydrolase, the enzyme that controls intracellular anandamide levels. A quantitative assay to determine whether anandamide was involved in bovine sperm-oviduct interaction was developed. R(C)-methanandamide, a non-hydrolysable anandamide analog, inhibited sperm binding to and induced sperm release from oviductal epithelia. Selective CB1 antagonists (SR141716A or AM251) completely blocked R(C)-methanandamide effects. However, SR144528, a selective CB2 antagonist, did not exert any effect, indicating that only CB1 was involved in R(C)-methanandamide effect. This effect was not caused by inhibition of the sperm progressive motility or by induction of the acrosome reaction. Overall, our findings indicate for the first time that the endocannabinoid system is present in bovine sperm and oviductal epithelium and that anandamide modulates the sperm-oviduct interaction, by inhibition of sperm binding and induction of sperm release from oviductal epithelial cells, probably by activating CB1 receptors.

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Section: Discussionsupporting

confidence: 77%

Section: Experiments 1 (Co-incubations)mentioning

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The endocannabinoid system in bull sperm and bovine oviductal epithelium: role of anandamide in sperm–oviduct interaction

Gervasi¹,

Rapanelli²,

Ribeiro³

et al. 2009

Reproduction

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“…2-AG, 2-arachidonoylglycerol; MTT, methylthiazolyldiphenyltetrazolium bromide; LDH, lactate dehydrogenase. homoeostasis are related to infertility and miscarriages (Paria et al 1996, Wang et al 2003, Schuel 2006, Fonseca et al 2010. The metabolic enzymes of AEA (NAPE-PLD and FAAH) have already been characterized in human placenta (Kenney et al 1999, Park et al 2003, Helliwell et al 2004, Habayeb et al 2008, Trabucco et al 2009, Taylor et al 2011, and it has also been reported that AEA induces a decrease in BeWo cell viability through the activation of CB2 receptor (Habayeb et al 2008).…”

Section: Discussionmentioning

confidence: 99%

2-Arachidonoylglycerol effects in cytotrophoblasts: metabolic enzymes expression and apoptosis in BeWo cells

Costa¹,

Fonseca²,

Keating³

et al. 2014

Reproduction

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The major endocannabinoid (eCB) 2-arachidonoylglycerol (2-AG) is a member of the endocannabinoid system (ECS) that participates in cell proliferation and apoptosis, important events for the homoeostasis of biological systems. The formation of placenta is one of the most important stages of pregnancy and its development requires highly regulated proliferation, differentiation and apoptosis of trophoblasts. Anomalies in these processes are associated with gestational pathologies. In this work, we aimed to study the involvement of 2-AG in cytotrophoblast cell turnover. We found that 2-AG biosynthetic (diacylglycerol lipase A) and degradative (monoacylglycerol lipase) enzymes are expressed in human cytotrophoblasts and in BeWo cells. We also found that 2-AG induces a decrease in cell viability in a time-and concentration-dependent manner and exerts antiproliferative effects. The loss of cell viability induced by a 48-h treatment with 2-AG (10 mM) was accompanied by chromatin fragmentation and condensation, morphological features of apoptosis. Additionally, 2-AG induced an increase in caspase 3/7 and 9 activities, a loss of mitochondrial membrane potential (Djm) and an increase in reactive oxygen species (ROS)/reactive nitrogen species (RNS) generation, suggesting the activation of the mitochondrial pathway. Moreover, whereas Djm loss and ROS/RNS generation were significantly attenuated by the antagonists of both the cannabinoid receptors 1 and 2 (CB1 and CB2), the increase in caspase 3/7 and 9 activities and loss of cell viability were reversed only by the antagonist of CB2 receptor; the blockage of the eCB membrane transporter and the depletion of cholesterol failed to reverse the effects of 2-AG. Therefore, this work supports the importance of cannabinoid signalling during cytotrophoblast cell turnover and that its deregulation may be responsible for altered placental development and poor pregnancy outcomes.

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Fatty Acid Amide Hydrolase: From Characterization to Therapeutics

Labar

Michaux

2007

Chemistry & Biodiversity

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Fatty acid amide hydrolase (FAAH) is an integral membrane enzyme within the amidase-signature family that terminates the action of several endogenous lipid messengers, including oleamide and the endocannabinoid anandamide. The hydrolysis of such messengers leads to molecules devoid of biological activity, and, therefore, modulates a number of neurobehavioral processes in mammals, including pain, sleep, feeding, and locomotor activity. Investigations into the structure and function of FAAH, its biological and therapeutic implications, as well as a description of different families of FAAH inhibitors are the topic of this review.

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Tuning the oviduct to the anandamide tone

Cited by 43 publications

References 14 publications

The endocannabinoid system in bull sperm and bovine oviductal epithelium: role of anandamide in sperm–oviduct interaction

The endocannabinoid system in bull sperm and bovine oviductal epithelium: role of anandamide in sperm–oviduct interaction

2-Arachidonoylglycerol effects in cytotrophoblasts: metabolic enzymes expression and apoptosis in BeWo cells

Fatty Acid Amide Hydrolase: From Characterization to Therapeutics

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