scholarly journals Decreased Expression of Cannabinoid Receptors in the Eutopic and Ectopic Endometrium of Patients with Adenomyosis

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Xue Shen ◽  
Hua Duan ◽  
Sha Wang ◽  
Lu Gan ◽  
Qian Xu ◽  
...  
Keyword(s):  
Cannabinoid Receptors ◽  
Negative Impact ◽  
Expression Patterns ◽  
Endocannabinoid System ◽  
Premenopausal Women ◽  
Mrna Levels ◽  
Secretory Phase ◽  
Normal Endometrium ◽  
Polymerase Chain ◽  
Ectopic Endometrium

Objective. Adenomyosis is a common gynecologic benign disease that may have a life-long negative impact on women. Previous studies have indicated that the endocannabinoid system may participate in the progress of endometriosis. Our research aims to analyze the expression patterns of the typical cannabinoid receptors (CB1 and CB2), the main constituents of the endocannabinoid system, in endometrial samples derived from patients diagnosed as adenomyosis or not. Methods. Eutopic and corresponding ectopic endometrium from 45 premenopausal women diagnosed as adenomyosis and normal endometrium from 34 age-matched women lacking evidence of adenomyosis were examined by immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR) to determine the CB1 and CB2 expression levels. Results. In either the proliferative or the secretory phase, CB1 and CB2 protein and mRNA levels were both significantly lower in the eutopic and ectopic endometrium of adenomyosis when compared with normal endometrium. For women with adenomyosis, CB1 and CB2 protein and mRNA levels were much lower in the ectopic endometrium than the eutopic in both phases of the cycle. Both CB1 and CB2 protein and mRNA levels were increased during the secretory phase in normal endometrium, while CB1 lost its cyclic variation in the eutopic and ectopic endometrium from patients diagnosed as adenomyosis. Conclusion. The decreased expression of CB1 and CB2 in the eutopic and ectopic endometrium from patients diagnosed as adenomyosis suggests that cannabinoid receptors may participate in the pathogenesis of adenomyosis.

scholarly journals The role of SRC1 and SRC2 in steroid-induced SDF1 expression in normal and ectopic endometrium

Reproduction ◽  
2014 ◽  
Vol 147 (6) ◽  
pp. 847-853 ◽  
Author(s):  
Xiu Shi ◽  
Wei Xu ◽  
Hui-Hua Dai ◽  
Ying Sun ◽  
Xiu-Li Wang
Keyword(s):  
Expression Patterns ◽  
Boyden Chamber ◽  
Mrna Levels ◽  
Cxcl12 Expression ◽  
Normal Endometrium ◽  
Endometrial Stromal Cells ◽  
Before And After ◽  
Stromal Cell Derived Factor ◽  
Steroid Receptor Coactivators ◽  
Ectopic Endometrium

To compare the expression patterns of steroid receptor coactivators (SRCs) and steroid-induced stromal cell-derived factor 1 (CXCL12 (SDF1)) in normal and ectopic endometrium and to explore the roles of NCOA1 (SRC1) and NCOA2 (SRC2) in the steroid-induced CXCL12 expression in normal and ectopic endometrial stromal cells (ESCs). The NCOA1, NCOA2, NCOA3 (SRC3), and CXCL12 (SDF1)α mRNA levels in normal and ectopic endometrium were analyzed by quantitative real-time PCR. Steroid-induced CXCL12 expression was detected by the ELISA method and the chemotactic activity of conditioned supernatant to monocyte was assessed by the Boyden chamber method before and after the silencing of NCOA1 or NCOA2 with siRNA in normal and ectopic ESCs. The expression of NCOA1 and CXCL12 in ectopic endometrium was significantly greater than that in normal endometrium in the secretory phase. Progesterone (P4) was able to significantly inhibit estradiol (E2)-stimulated CXCL12 expression in normal and ectopic ESCs. The inhibitory rate of P4 in ectopic ESCs at 72 and 96 h was significantly lower than that in normal ESCs. Silencing of NCOA1 but not NCOA2 significantly reduced the E2-induced CXCL12 expression in normal and ectopic ESCs. The ability of P4 to inhibit E2-induced CXCL12 expression and monocyte chemotaxis in normal and ectopic ESCs was significantly attenuated when NCOA2 was silenced. NCOA1 plays a necessary role in E2-induced CXCL12 expression and NCOA2 is required for P4 to inhibit the E2-induced CXCL12 production in normal and ectopic endometrium.

scholarly journals GDF-9 and BMP-15 mRNA Levels in Canine Cumulus Cells Related to Cumulus Expansion and the Maturation Process

Animals ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 462 ◽  
Author(s):  
George Ramirez ◽  
Jaime Palomino ◽  
Karla Aspee ◽  
Monica De los Reyes
Keyword(s):  
Gene Expression ◽  
Estrous Cycle ◽  
Expression Patterns ◽  
Cumulus Cells ◽  
Mrna Levels ◽  
Cumulus Expansion ◽  
Polymerase Chain ◽  
Specific Regulation ◽  
Reproductive Phases

The competence to undergo expansion is a characteristic of cumulus cells (CCs). The aim was to investigate the expression of GDF-9 and BMP-15 mRNA in canine cumulus cells in relation to cumulus expansion and meiotic development over the estrous cycle. CCs were recovered from nonmatured and in vitro-matured (IVM) dog cumulus oocyte complexes (COCs), which were obtained from antral follicles at different phases of the estrous cycle. Quantitative real-time polymerase chain reaction (q-PCR) was used to evaluate the relative abundance of GDF-9 and BMP-15 transcripts from the CCs with or without signs of expansion. The results were evaluated by ANOVA and logistic regression. The maturity of the oocyte and the expansion process affected the mRNA levels in CCs. There were differences (p < 0.05) in GDF-9 and BMP-15 gene expression in CCs isolated from nonmatured COCs when comparing the reproductive phases. Lower mRNA levels (p < 0.05) were observed in anestrus and proestrus in comparison to those in estrus and diestrus. In contrast, when comparing GDF-9 mRNA levels in IVM COCs, no differences were found among the phases of the estrous cycle in expanded and nonexpanded CCs (p < 0.05). However, the highest (p < 0.05) BMP-15 gene expression in CCs that did not undergo expansion was exhibited in anestrus and the lowest (p < 0.05) expression was observed in estrus in expanded CCs. Although the stage of the estrous cycle did not affect the second metaphase (MII )rates, the expanded CCs obtained at estrus coexisted with higher percentages of MII (p < 0.05). In conclusion, the differential expression patterns of GDF-9 and BMP-15 mRNA transcripts might be related to cumulus expansion and maturation processes, suggesting specific regulation and temporal changes in their expression.

scholarly journals Endocannabinoid System in Hepatic Glucose Metabolism, Fatty Liver Disease, and Cirrhosis

2019 ◽  
Vol 20 (10) ◽  
pp. 2516 ◽  
Author(s):  
Ivonne Bazwinsky-Wutschke ◽  
Alexander Zipprich ◽  
Faramarz Dehghani
Keyword(s):  
Insulin Resistance ◽  
Portal Hypertension ◽  
Liver Disease ◽  
Glucose Metabolism ◽  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Expression Patterns ◽  
Endocannabinoid System ◽  
Hepatic Glucose Metabolism ◽  
Hepatic Glucose

There is growing evidence that glucose metabolism in the liver is in part under the control of the endocannabinoid system (ECS) which is also supported by its presence in this organ. The ECS consists of its cannabinoid receptors (CBRs) and enzymes that are responsible for endocannabinoid production and metabolism. ECS is known to be differentially influenced by the hepatic glucose metabolism and insulin resistance, e.g., cannabinoid receptor type 1(CB1) antagonist can improve the glucose tolerance and insulin resistance. Interestingly, our own study shows that expression patterns of CBRs are influenced by the light/dark cycle, which is of significant physiological and clinical interest. The ECS system is highly upregulated during chronic liver disease and a growing number of studies suggest a mechanistic and therapeutic impact of ECS on the development of liver fibrosis, especially putting its receptors into focus. An opposing effect of the CBRs was exerted via the CB1 or CB2 receptor stimulation. An activation of CB1 promoted fibrogenesis, while CB2 activation improved antifibrogenic responses. However, underlying mechanisms are not yet clear. In the context of liver diseases, the ECS is considered as a possible mediator, which seems to be involved in the synthesis of fibrotic tissue, increase of intrahepatic vascular resistance and subsequently development of portal hypertension. Portal hypertension is the main event that leads to complications of the disease. The main complication is the development of variceal bleeding and ascites, which have prognostic relevance for the patients. The present review summarizes the current understanding and impact of the ECS on glucose metabolism in the liver, in association with the development of liver cirrhosis and hemodynamics in cirrhosis and its complication, to give perspectives for development of new therapeutic strategies.

scholarly journals Investigation of Tenascin Expression in Endometriosis

2012 ◽  
Vol 2012 ◽  
pp. 1-5
Author(s):  
Zehra Sema Ozkan ◽  
Hasan Cilgin ◽  
Remzi Atilgan ◽  
Mehmet Simsek ◽  
Bengu Cobanoglu ◽  
...  
Keyword(s):  
Matrix Protein ◽  
Expression Patterns ◽  
Serum Levels ◽  
Extracellular Matrix Protein ◽  
Secretory Phase ◽  
Tissue Samples ◽  
Intense Staining ◽  
Tissue Levels ◽  
Significant Difference ◽  
Ectopic Endometrium

Objective. To evaluate the serum and tissue levels and local expression pattern of tenascin, a high molecular weight extracellular matrix protein, in eutopic and ectopic endometrium from patients with and without endometriosis and to compare the proliferative and secretory phase differences. Materials and Methods. Thirty women with endometriosis and fifteen women without endometriosis undergoing surgery for benign indications were included in the study. Serum and tissue levels and proliferative and secretory phase expression patterns of tenascin in the ectopic and eutopic endometrium were analyzed with immunohistochemistry and immunoassays. The results were compared with Mann-Whitney U test. P values <0.05 were considered as statistically significant. Results. Tenascin expression was detected in both of eutopic and ectopic endometrium of women with and without endometriosis. In immunohistochemical staining, intense staining of tenascin was observed in glandular cells of eutopic and ectopic endometrial tissue samples of both groups during secretory phase (P<0.01). Eutopic and ectopic tissue levels of tenascin were higher than serum tenascin levels only secretory phase (P=0.02). There was no significant difference between groups for tissue and serum levels of tenascin during cycle phases. Conclusion. Tenascin expression showed cyclic change on eutopic and ectopic endometrium.

Gene and protein expression of connexins 37 and 43 in cumulus–oocytes complexes throughout the canine oestrous cycle

2020 ◽  
Vol 32 (11) ◽  
pp. 976
Author(s):  
Monica De los Reyes ◽  
Jaime Palomino ◽  
Carola Gallegos ◽  
Roberto Espinoza ◽  
Phillipe Dettleff ◽  
...  
Keyword(s):  
Quantitative Polymerase Chain Reaction ◽  
Expression Patterns ◽  
Cumulus Cells ◽  
Oestrous Cycle ◽  
Mrna Levels ◽  
Chain Reaction ◽  
Antral Follicles ◽  
Gene And Protein Expression ◽  
Before And After ◽  
Polymerase Chain

The aim of this study was to evaluate the expression of connexin (Cx) 37 and Cx43 in canine cumulus–oocyte complexes (COCs) during the oestrous cycle. Cx localisation was analysed by immunohistochemistry and immunofluorescence, whereas protein and gene expression was evaluated by western blotting and quantitative polymerase chain reaction respectively; comparisons were made using analysis of variance. Both Cx37 and Cx43 were expressed in all follicular stages; Cx43 was identified in cumulus cells and Cx37 was identified in cumulus cells, zonae pellucida and oocytes. Immunofluorescence analyses showed that Cx37 remained unchanged during the preovulatory stage but decreased after ovulation, whereas Cx43 remained unchanged before and after ovulation. Cx43 transcripts increased (P&lt;0.05) during anoestrus and dioestrus in medium-sized follicles but remained unaltered during the pro-oestrus and antral stages during oestrus, before and after ovulation. Cx37 mRNA levels decreased in ovulated COCs (P&lt;0.05). The highest levels of Cx37 protein (P&lt;0.05) were detected in the preantral stage during anoestrus. In contrast, strong Cx43 signals were detected in oestrus and in medium-sized antral follicles in dioestrus (P&lt;0.05). Overall, we demonstrated that Cx37 and Cx43 exhibit different expression patterns, suggesting specific roles throughout growth. Maintenance of Cx expression before ovulation indicates the involvement of Cx37 and Cx43 in the prolonged meiotic arrest.

scholarly journals Nuclear factor κB pathway and interleukin-6 are affected in eutopic endometrium of women with endometriosis

Reproduction ◽  
2009 ◽  
Vol 137 (4) ◽  
pp. 727-737 ◽  
Author(s):  
Carlos Ponce ◽  
Marisa Torres ◽  
Carolina Galleguillos ◽  
Hugo Sovino ◽  
M Angélica Boric ◽  
...  
Keyword(s):  
Interleukin 6 ◽  
Nuclear Factor Κb ◽  
Mrna Levels ◽  
Nuclear Factor ◽  
Secretory Phase ◽  
Normal Endometrium ◽  
Eutopic Endometrium ◽  
Iκb Kinase ◽  
Nfkb Pathway ◽  
Late Secretory Phase

In order to investigate the role of the nuclear factor κB (NFKB) pathway on gene expression in the eutopic endometrium in endometriosis, and in particular of interleukin-6 (IL6), we evaluated RELA, IκB kinase (CHUK), NFKBIA and IL6 expressions and NFKB DNA binding in eutopic endometrium from women with endometriosis. Eutopic endometrium was obtained from 37 women with endometriosis and 42 fertile women during laparoscopy. We analysed RELA, CHUK, NFKBIA and IL6 mRNA levels (RT-PCR); RELA, CHUK and NFKBIA proteins and p-NFKBIA/NFKBIA ratio (western blot); and NFKB binding (DNA shift assay) and IL6 concentration (ELISA) in endometrial explants. Our results indicate that mRNA and cytoplasmic proteins of RELA and CHUK exhibit constant levels in normal endometrium during the menstrual cycle. A dramatic increase (P<0.05) in NFKBIA mRNA expression, RELA nuclear presence and the mRNA and the protein of IL6 during late secretory phase was also observed in this tissue. By contrast, in eutopic endometrium from endometriosis patients, a decrease (P<0.05) in IL6 mRNA and protein (61%), NFKBIA mRNA (46%), p-NFKBIA/NFKBIA ratio (42%), RELA nuclear stromal (68%) and CHUK (48%) proteins were found exclusively during the late secretory phase compared with normal endometrium. In conclusion, the canonical activation of NFKB pathway is deregulated and may have reduced transcriptional function affecting NFKBIA and IL6 expression, genes related local proinflammatory processes. These molecular alterations observed during the late secretory phase in eutopic endometrium from endometriosis patients constitute a NFKB system dysfunction, suggesting that NFKB could be an important factor in endometriosis aetiology.

scholarly journals Footshock-Induced Abstinence from Compulsive Methamphetamine Self-administration in Rat Model Is Accompanied by Increased Hippocampal Expression of Cannabinoid Receptors (CB1 and CB2)

2022 ◽  
Author(s):  
Subramaniam Jayanthi ◽  
Ritvik Peesapati ◽  
Michael T. McCoy ◽  
Bruce Ladenheim ◽  
Jean Lud Cadet
Keyword(s):  
Substance Use ◽  
Synaptic Plasticity ◽  
Substance Use Disorders ◽  
Rat Model ◽  
Cognitive Functions ◽  
Cannabinoid Receptors ◽  
Endocannabinoid System ◽  
Mrna Levels ◽  
Self Administration ◽  
Punishment Phase

AbstractMethamphetamine (METH) use disorder (MUD) is characterized by compulsive and repeated drug taking despite negative life consequences. Large intake of METH in humans and animals is accompanied by dysfunctions in learning and memory processes. The endocannabinoid system (ECS) is known to modulate synaptic plasticity and cognitive functions. In addition, the ECS has been implicated in some of the manifestations of substance use disorders (SUDs). We therefore sought to identify potential changes in the expression of various enzymes and of the receptors (CB1 and CB2) that are members of that system. Herein, we used a model of METH self-administration (SA) that includes a punishment phase (footshocks) that helps to separate rats into a compulsive METH phenotype (compulsive) that continues to take METH and a non-compulsive METH (abstinent) group that suppressed or stopped taking METH. Animals were euthanized 2 h after the last METH SA session and their hippocampi were used to measure mRNA levels of cannabinoid receptors (CB/Cnr), as well as those of synthesizing (DAGL-A, DAGL-B, NAPEPLD) and metabolizing (MGLL, FAAH, PTGS2) enzymes of the endocannabinoid cascade. Non-compulsive rats exhibited significant increased hippocampal expression of CB1/Cnr1 and CB2/Cnr2 mRNAs. mRNA levels of the synthesizing enzyme, DAGL-A, and of the metabolic enzymes, MGLL and FAAH, were also increased. Non-compulsive rats also exhibited a significant decrease in hippocampal Ptgs2 mRNA levels. Taken together, these observations implicate the hippocampal endocannabinoid system in the suppression of METH intake in the presence of adverse consequences.

P4140Myeloid but not endothelial expression of the CB2 receptor promotes atherogenesis in the context of elevated levels of the endocannabinoid 2-arachidonoylglycerol

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
J Jehle ◽  
E Avraamidou ◽  
M Danisch ◽  
S Bagheri ◽  
B Schoene ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Mouse Models ◽  
Plasma Levels ◽  
Cannabinoid Receptors ◽  
Endocannabinoid System ◽  
Receptor Expression ◽  
Mrna Levels ◽  
Cb2 Receptor ◽  
Deficient Mice

Abstract Background The endocannabinoid 2-arachidonoylglycerol (2-AG) is an inflammatory mediator and ligand to the cannabinoid receptors CB1 and CB2, which are expressed on myeloid and endothelial cells. 2-AG has recently been described to promote atherogenesis in ApoE-deficient mice. While the CB2 receptor has previously been considered to solely exert anti-inflammatory and atheroprotective effects, newer data have raised the notion, that CB2 might exert atherogenic effects in the context of elevated 2-AG plasma levels. In the present study, we investigated the atherogenic mechanisms of 2-AG and the role of the CB2 receptor on myeloid and endothelial cells in atherogenesis using cell-specific knockout mouse models. Methods Two mouse models with atherogenic background and distinct cell-specific knockouts of the CB2 receptor on myeloid (ApoE−/−LysMcreCB2fl/fl) or endothelial cells (ApoE−/−Tie2creCB2fl/fl) were created. Mice were treated with JZL184, which inhibits 2-AG-degrading enzyme monoacylglycerol lipase, and thereby elevates 2-AG plasma levels, or with vehicle (DMSO), while being fed a high-fat diet for four weeks. Plaque volume and plaque composition were analyzed. In vitro, macrophages were treated with 2-AG and mRNA levels of adhesion molecules, scavenger receptors and chemokines, the production of reactive oxygen species (ROS) and the release of myeloperoxidase (MPO) were determined using qPCR, fluorometric assays and ELISA respectively. Results Elevated levels of 2-AG promote atherogenesis in ApoE-deficient mice (JZL184 vs. DMSO: 39.6±2.1% vs. 32.6±2.4%; n=14; p<0.05). The atherogenic effect of 2-AG is abrogated in mice lacking myeloid CB2 receptor expression (35.0±2.0% vs. 34.0±2.5%; n=14–16; p>0.05) but not in mice lacking endothelial CB2 receptor expression (37.1±3.1% vs. 20.9±2.6%; n=10–12; p<0.01). In vitro, 2-AG significantly increases transcription of adhesion molecule ICAM-1 (2.09±0.42 –fold; n=5–6; p<0.05), chemokine receptor CCR-1 (2.04±0.46 -fold; n=10–11; p<0.05) and scavenger receptor CD36 (8.02±1.89-fold; n=3; p<0.05) in 2-AG-treated macrophages. These effects are mitigated by pharmacological inhibition of CB2. Furthermore, 2-AG significantly increases myeloperoxidase (MPO) release in monocytes in a CB receptor-dependent fashion (451±23 pg/ml vs. 151±8.3 pg/ml; n=3–4; p<0.01) and promotes ROS production (2698±24 pdu vs. 1981±27 pdu; n=8; p<0.01). Conclusion Elevated 2-AG levels show an atherogenic effect in vivo which is dependent on the presence of the CB2 receptor on myeloid cells. Our in vitro data reveal 2-AG to promote pro-inflammatory signaling in macrophages and elucidate a previously unrecognized link between the endocannabinoid system and MPO in monocytes. In summary, cell-specific effects of the endocannabinoid system will have to be taken into account to facilitate its exploitation as an anti-atherosclerotic drug target. Acknowledgement/Funding This work was supported by the Bonfor program of the University of Bonn [grant number O-109.0057 to JJ].

scholarly journals Role of the endocannabinoid system in the mechanisms involved in the LPS-induced preterm labor

Reproduction ◽  
2015 ◽  
Vol 150 (6) ◽  
pp. 463-472 ◽  
Author(s):  
María Victoria Bariani ◽  
Ana Paula Domínguez Rubio ◽  
Maximiliano Cella ◽  
Juliana Burdet ◽  
Ana María Franchi ◽  
...  
Keyword(s):  
Preterm Labor ◽  
Cannabinoid Receptors ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Endocannabinoid System ◽  
Preterm Births ◽  
Intrauterine Infection ◽  
Mrna Levels ◽  
Uterine Contractions ◽  
Amide Hydrolase

Prematurity is the leading cause of perinatal morbidity and mortality worldwide. There is a strong causal relationship between infection and preterm births. Intrauterine infection elicits an immune response involving the release of inflammatory mediators like cytokines and prostaglandins (PG) that trigger uterine contractions and parturition events. Anandamide (AEA) is an endogenous ligand for the cannabinoid receptors CB1 and CB2. Similarly to PG, endocannabinoids are implicated in different aspects of reproduction, such as maintenance of pregnancy and parturition. Little is known about the involvement of endocannabinoids on the onset of labor in an infectious milieu. Here, using a mouse model of preterm labor induced by lipopolysaccharide (LPS), we explored changes on the expression of components of endocannabinoid system (ECS). We have also determined whether AEA and CB antagonists alter PG production that induces labor. We observed an increase in uterineN-acylphosphatidylethanolamine-specific phospholipase D expression (NAPE-PLD, the enzyme that synthesizes AEA) upon LPS treatment. Activity of catabolic enzyme fatty acid amide hydrolase (FAAH) did not change significantly. In addition, we also found that LPS modulated uterine cannabinoid receptors expression by downregulatingCb2mRNA levels and upregulating CB1 protein expression. Furthermore, LPS and AEA induced PGF2a augmentation, and this was reversed by antagonizing CB1 receptor. Collectively, our results suggest that ECS may be involved in the mechanism by which infection causes preterm birth.

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