Endocannabinoids as endometrial inflammatory markers in lactating Holstein cows

Bonsale, R; Sharifi, Reza; Dirandeh, E.; Hedayat, Nemat; Mojtahedin, Ali; Ghorbanalinia, M; Abolghasemi, Armita

doi:10.1111/rda.13169

Cited by 17 publications

(6 citation statements)

References 42 publications

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“…Increased gene expression of the cannabinoid receptors following treatment with an antagonist such as LPS was demonstrated in many cell types, not just immune mediating cells. Expression patterns of ECS related genes observed in this study agree with endometrial expression of ECS related genes in Holstein dairy cows suffering from endometritis [ 10 ] and expression of hypothalamic ECS genes in Holstein dairy cows experiencing metabolic stress due to onset of lactation [ 19 ]. Therefore, elevated synthesis or release of AEA and receptor expression reported in this study, support involvement of the ECS in inflammatory regulation of BAEC.…”

Section: Discussionsupporting

confidence: 80%

“…As part of the endocannabinoid system (ECS), EC and dedicated cannabinoid receptors-1 and -2 (CB1/2), are involved in several physiological processes, such as energy homeostasis, cellular metabolism, pain, and inflammation [ 9 ]. Fluctuations of EC plasma concentrations during inflammatory events in dairy cows has recently been demonstrated [ 10 ] and elevated concentrations of arachidonoylethanolamide, or anandamide (AEA) associated with non-steroidal anti-inflammatory drug (NSAID) treatment in murine models, is theorized to contribute to the analgesic effects of the drugs [ 11 ]. Considering that in isolated endothelial and other immune mediating cells, effects of AEA not only vary by tissue type but are highly time and concentration dependent [ 12 ], increased AEA concentrations can lead to elevated ROS production, mitochondrial dysfunction, prolonged activation of macrophages and neutrophils, as well as induction of apoptotic signaling via cannabinoid receptors 1 and 2 (CB1/2) [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

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Anandamide Alters Barrier Integrity of Bovine Vascular Endothelial Cells during Endotoxin Challenge

2022

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Vascular endothelial cells are crucial mediators of inflammation during infectious diseases, due to their ability to produce lipid-based inflammatory mediators and facilitate leukocyte migration and translocation to infected tissues. Mastitis is the costliest infectious disease in North America, with over two billion dollars in annual costs due to loss of milk production, medical treatment, and potential loss of the animal. Infections caused by coliform bacteria are particularly deleterious, causing a negative impact on cow well-being and a high mortality rate. Dysfunction and breakdown of the endothelial barrier is a key part of the pathology of coliform mastitis. The endocannabinoid system (ECS), shown to modulate inflammatory responses of vascular endothelial cells in humans and rodents, may be a novel target for inflammatory modulation in dairy cows. The endocannabinoid (EC) arachidonoylethanolamide (AEA) is a potent anti- or pro-inflammatory mediator in endothelial cells, depending on location, timing, and concentration. We hypothesized that elevated AEA during LPS challenge will impair endothelial barrier integrity via increased production of reactive oxygen species (ROS) and activation of apoptotic pathways. Challenge of bovine aortic endothelial cells (BAEC) with 25 ng/mL lipopolysaccharide (LPS) for 8 h induced AEA synthesis, increased expression of cannabinoid receptor 1 and 2 (CB1/2) and the AEA synthesizing enzyme N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD), while decreasing gene expression of the AEA degradation enzyme fatty acid amide hydrolase (FAAH). Trans endothelial resistance (TER), measured through electrical resistance across the monolayer, increased 2 h after 0.5 µM AEA treatment and decreased with 5 µM AEA, compared to LPS alone. Addition of AEA to BAEC challenged with LPS induced mitochondrial dysfunction via increased ROS production, cytochrome-C release, and activation of caspase 3/7. Antagonism of CB1 by 1 µM AM251 ameliorated AEA induced ROS production and cytochrome-C release. Addition of AM251 also eliminated 2 h TER increase and improved TER following 5 µM AEA. Doses of 0.5, 1, and 5 µM AEA delayed endothelial barrier recovery, which was eliminated by the addition of AM251. Mitochondrial dysfunction and activation of apoptotic pathways in response to AEA treatment during LPS challenge of BAEC may act to delay inflammatory resolution and contribute to endothelial dysfunction.

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Section: Discussionsupporting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Anandamide Alters Barrier Integrity of Bovine Vascular Endothelial Cells during Endotoxin Challenge

2022

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“…In contrast, IL10 is a cytokine with potent anti-inflammatory properties and was not overly expressed supporting overall coordination of sustaining an inflammatory environment in cows that experienced embryonic loss. Prolonged inflammation and its carryover effects impair immune status and reproductive performance of dairy cows 11 , 33 . Up-regulation of genes associated with the pro-inflammatory cascade ( TLR2, TLR4 and IL1B ) in peripheral blood of leucocytes in cows at 16 days after TAI was evident in cows with embryonic loss compared with pregnant cows.…”

Section: Discussionmentioning

confidence: 99%

Peripheral leucocyte molecular indicators of inflammation and oxidative stress are altered in dairy cows with embryonic loss

Dirandeh

Sayyar

Pirsaraei

et al. 2021

Sci Rep

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Objective of experiment was to determine whether oxidative stress (OS) and inflammation altered embryonic loss in dairy cows. Blood samples were collected at days 0, 16, 32 and 60 after timed (AI) from 200 Holstein cows to determine embryonic loss based on interferon-stimulated gene-15 (ISG15) mRNA expression (day 16) and ultrasound at day 32 and day 60. Leucocyte expressions of mRNA TLR2, TLR4, TNF-α, IL1B, IL10, STAT3 (inflammation), PTGS2, PTGES (prostaglandin synthesis), and PLA2G4A and ALOX5AP (eicosanoid metabolism) at days 0 and 16 were determined. Plasma redox status for antioxidant enzymatic activities of glutathione peroxidase (GPX), superoxide dismutase (SOD), total antioxidant capacity (TAC), and concentrations of malondialdehyde (MDA) were determined at days 0, 16, 32 and 60. All antioxidant-redox responses were beneficially significant in pregnant cows diagnosed pregnant at day16 and sustained pregnancy to day 60 compared to non-pregnant cows at day16 or pregnant at day16 and lost embryos by days 32 or 60. The leucocyte mRNA expressions of TLR2, TLR4, STAT 3, IL1B, PTGS2, PLA2G4A and ALOX5AP were greater and PTGES was lower at day16 in pregnant cows that lost embryos early (P < 0.05). In conclusion peripheral leucocyte molecular indicators of inflammation and plasma indicators of OS were altered in pregnant cows undergoing embryonic losses compared to cows with a sustained pregnancy.

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“…In support of this, the circulating TNFα levels in HWL cows were higher than in their LWL counterparts throughout the transition period ( P < 0.05), found in a companion study with a similar design (unpublished data). Recently, increased relative mRNA expressions of the eCB synthesizing enzyme NAPEPLD and of the CNR2 receptor, as well as reduced mRNA expressions of the eCB hydrolyzing enzymes, N-acylethanolamine acid amidase and FAAH, were found in endometrium; this was associated with the inflammatory state of these cows[ 54 ]. This suggests that tissue eCBs may be increased during inflammation, which is in agreement with our findings of increased eCBs related to inflammation and lipolysis in AT of PP HWL cows.…”

Section: Discussionmentioning

confidence: 99%

Characterization of the endocannabinoid system in subcutaneous adipose tissue in periparturient dairy cows and its association to metabolic profiles

et al. 2018

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Adipose tissue (AT) plays a major role in metabolic adaptations in postpartum (PP) dairy cows. The endocannabinoid (eCB) system is a key regulator of metabolism and energy homeostasis; however, information about this system in ruminants is scarce. Therefore, this work aimed to assess the eCB system in subcutaneous AT, and to determine its relation to the metabolic profile in peripartum cows. Biopsies of AT were performed at 14 d prepartum, and 4 and 30 d PP from 18 multiparous peripartum cows. Cows were categorized retrospectively according to those with high body weight (BW) loss (HWL, 8.5 ± 1.7% BW loss) or low body weight loss (LWL, 2.9 ± 2.5% BW loss) during the first month PP. The HWL had higher plasma non-esterified fatty acids and a lower insulin/glucagon ratio PP than did LWL. Two-fold elevated AT levels of the main eCBs, N-arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG), were found 4 d PP compared with prepartum in HWL, but not in LWL cows. AT levels of the eCB-like molecules oleoylethanolamide, palmitoylethanolamide, and of arachidonic acid were elevated PP compared with prepartum in all cows. The abundance of monoglyceride lipase (MGLL), the 2-AG degrading enzyme, was lower in HWL vs. LWL AT PP. The relative gene expression of the cannabinoid receptors CNR1 and CNR2 in AT tended to be higher in HWL vs. LWL PP. Proteomic analysis of AT showed an enrichment of the inflammatory pathways’ acute phase signaling and complement system in HWL vs. LWL cows PP. In summary, eCB levels in AT were elevated at the onset of lactation as part of the metabolic adaptations in PP dairy cows. Furthermore, activating the eCB system in AT is most likely associated with a metabolic response of greater BW loss, lipolysis, and AT inflammation in PP dairy cows.

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Endocannabinoids as endometrial inflammatory markers in lactating Holstein cows

Cited by 17 publications

References 42 publications

Anandamide Alters Barrier Integrity of Bovine Vascular Endothelial Cells during Endotoxin Challenge

Anandamide Alters Barrier Integrity of Bovine Vascular Endothelial Cells during Endotoxin Challenge

Peripheral leucocyte molecular indicators of inflammation and oxidative stress are altered in dairy cows with embryonic loss

Characterization of the endocannabinoid system in subcutaneous adipose tissue in periparturient dairy cows and its association to metabolic profiles

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