Omega-3 fatty acid supplementation from late pregnancy to early lactation attenuates the endocannabinoid system and immune proteome in preovulatory follicles and endometrium of Holstein dairy cows
ABSTRACT: Activation of the endocannabinoid system (ECS) elicits negative effects on the reproductive system in mammals. Supplementation with n-3 fatty acid (FA) lowers ECS activation and has anti-inflammatory effects. Thus, we hypothesized that supplementing cows with n-3 FA will downregulate compo...
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Elsevier
2025-04-01
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| Series: | Journal of Dairy Science |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022030225000037 |
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| author | P. dos S. Silva Y. Butenko G. Kra S. Malitsky M. Itkin Y. Levin U. Moallem M. Zachut |
| author_facet | P. dos S. Silva Y. Butenko G. Kra S. Malitsky M. Itkin Y. Levin U. Moallem M. Zachut |
| author_sort | P. dos S. Silva |
| collection | DOAJ |
| description | ABSTRACT: Activation of the endocannabinoid system (ECS) elicits negative effects on the reproductive system in mammals. Supplementation with n-3 fatty acid (FA) lowers ECS activation and has anti-inflammatory effects. Thus, we hypothesized that supplementing cows with n-3 FA will downregulate components of the ECS and immune system in preovulatory follicles and in the endometrium. Twenty-four multiparous Holstein dairy cows were supplemented from d 256 of pregnancy to d 70 postpartum as follows: (1) control (CTL; n = 12), prepartum with 250 g/d per cow calcium salts of FA and postpartum at 1.6% of the diet (DM basis); or (2) extruded flaxseed (FLX; n = 12) supplement rich in α-linolenic acid (C18:3n-3), prepartum with 700 g/d per cow and postpartum at 6.4% of diet (DM basis). Ovaries were monitored at 30 DIM, and following estrous cycle synchronization we aspirated the follicular fluids (FF) of follicles ≥7 mm, separated the granulosa cells (GRC), and performed endometrium biopsies at 58 ± 5 DIM. The FF were analyzed for concentrations of estradiol (E2) and progesterone (P4), and E2-active follicles were declared when E2/P4 was >1. The FA and endocannabinoid (eCB) profiles were determined in plasma and in the reproductive tissues. Proteomic analyses and mRNA abundances were determined in GRC and endometrium. Supplementation of n-3 FA increased the proportion of total n-3 FA and decreased the ratio of n-6 to n-3 ratio in plasma, FF and GRC compared with CTL. In plasma and FF, n-3 FA supplementation decreased the proportion of the n-6 FA eCB precursor arachidonic acid (ARA; C20:4n-6), and increased the abundance of the n-3 FA-derived eCB eicosapentaenoyl ethanolamide compared with CTL. In the endometrium, n-3 FA supplementation reduced the abundance of the n-6 FA-derived eCB 2-arachidonoylglycerol (2-AG) compared with CTL. Proteomic analysis of GRC showed that n-3 FA supplementation increased the abundance of FA-binding-protein-5, which is involved in intracellular transport of eCB, as well as the abundances of the cytokine receptor like factor-2 and glutathione-S-transferase-LANCL1, whereas it reduced the abundances of several complement proteins: complement factors I, D, H, complement components C7 chain and C8 β chain, and complement component 1 Q subcomponent-binding protein, mitochondrial (C1QBP). In addition, the abundance of superoxide dismutase (SOD3) was lower in FLX GRC than in CTL. In the endometrium, n-3 FA supplementation decreased the abundance of a few immune-related proteins. In the GRC, n-3 FA supplementation reduced the relative mRNA abundances of cannabinoid receptors 1 and 2 compared with CTL. Across treatments, a positive correlation was found between the relative abundance in FF of the eCB anandamide with C7, C1QBP, and SOD3 in GRC, whereas FF 2-AG had a negative correlation with them. Overall, in line with our premise, dietary n-3 FA supplementation attenuated the levels of some eCB and reduced the expression of several proteins and genes related to the ECS and immune system in the preovulatory follicle and in the endometrium, which may be part of the etiology of the positive effects of n-3 FA on the reproductive system in dairy cows. |
| format | Article |
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| institution | OA Journals |
| issn | 0022-0302 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Elsevier |
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| series | Journal of Dairy Science |
| spelling | doaj-art-1d8a347c648f40439e0e5b6af45e58472025-08-20T02:27:34ZengElsevierJournal of Dairy Science0022-03022025-04-0110844299431710.3168/jds.2024-25409Omega-3 fatty acid supplementation from late pregnancy to early lactation attenuates the endocannabinoid system and immune proteome in preovulatory follicles and endometrium of Holstein dairy cowsP. dos S. Silva0Y. Butenko1G. Kra2S. Malitsky3M. Itkin4Y. Levin5U. Moallem6M. Zachut7Department of Ruminant Science, Institute of Animal Sciences, Agricultural Research Organization, Volcani Institute, 7505101 Rishon LeZion, Israel; Department of Animal Science, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, 7610001 Rehovot, IsraelDepartment of Ruminant Science, Institute of Animal Sciences, Agricultural Research Organization, Volcani Institute, 7505101 Rishon LeZion, IsraelDepartment of Ruminant Science, Institute of Animal Sciences, Agricultural Research Organization, Volcani Institute, 7505101 Rishon LeZion, Israel; Department of Animal Science, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, 7610001 Rehovot, IsraelLife Sciences Core Facilities, Weizmann Institute of Science, 7610001 Rehovot, IsraelLife Sciences Core Facilities, Weizmann Institute of Science, 7610001 Rehovot, IsraelThe Nancy and Stephen Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science, 7610001 Rehovot, IsraelDepartment of Ruminant Science, Institute of Animal Sciences, Agricultural Research Organization, Volcani Institute, 7505101 Rishon LeZion, IsraelDepartment of Ruminant Science, Institute of Animal Sciences, Agricultural Research Organization, Volcani Institute, 7505101 Rishon LeZion, Israel; Corresponding authorABSTRACT: Activation of the endocannabinoid system (ECS) elicits negative effects on the reproductive system in mammals. Supplementation with n-3 fatty acid (FA) lowers ECS activation and has anti-inflammatory effects. Thus, we hypothesized that supplementing cows with n-3 FA will downregulate components of the ECS and immune system in preovulatory follicles and in the endometrium. Twenty-four multiparous Holstein dairy cows were supplemented from d 256 of pregnancy to d 70 postpartum as follows: (1) control (CTL; n = 12), prepartum with 250 g/d per cow calcium salts of FA and postpartum at 1.6% of the diet (DM basis); or (2) extruded flaxseed (FLX; n = 12) supplement rich in α-linolenic acid (C18:3n-3), prepartum with 700 g/d per cow and postpartum at 6.4% of diet (DM basis). Ovaries were monitored at 30 DIM, and following estrous cycle synchronization we aspirated the follicular fluids (FF) of follicles ≥7 mm, separated the granulosa cells (GRC), and performed endometrium biopsies at 58 ± 5 DIM. The FF were analyzed for concentrations of estradiol (E2) and progesterone (P4), and E2-active follicles were declared when E2/P4 was >1. The FA and endocannabinoid (eCB) profiles were determined in plasma and in the reproductive tissues. Proteomic analyses and mRNA abundances were determined in GRC and endometrium. Supplementation of n-3 FA increased the proportion of total n-3 FA and decreased the ratio of n-6 to n-3 ratio in plasma, FF and GRC compared with CTL. In plasma and FF, n-3 FA supplementation decreased the proportion of the n-6 FA eCB precursor arachidonic acid (ARA; C20:4n-6), and increased the abundance of the n-3 FA-derived eCB eicosapentaenoyl ethanolamide compared with CTL. In the endometrium, n-3 FA supplementation reduced the abundance of the n-6 FA-derived eCB 2-arachidonoylglycerol (2-AG) compared with CTL. Proteomic analysis of GRC showed that n-3 FA supplementation increased the abundance of FA-binding-protein-5, which is involved in intracellular transport of eCB, as well as the abundances of the cytokine receptor like factor-2 and glutathione-S-transferase-LANCL1, whereas it reduced the abundances of several complement proteins: complement factors I, D, H, complement components C7 chain and C8 β chain, and complement component 1 Q subcomponent-binding protein, mitochondrial (C1QBP). In addition, the abundance of superoxide dismutase (SOD3) was lower in FLX GRC than in CTL. In the endometrium, n-3 FA supplementation decreased the abundance of a few immune-related proteins. In the GRC, n-3 FA supplementation reduced the relative mRNA abundances of cannabinoid receptors 1 and 2 compared with CTL. Across treatments, a positive correlation was found between the relative abundance in FF of the eCB anandamide with C7, C1QBP, and SOD3 in GRC, whereas FF 2-AG had a negative correlation with them. Overall, in line with our premise, dietary n-3 FA supplementation attenuated the levels of some eCB and reduced the expression of several proteins and genes related to the ECS and immune system in the preovulatory follicle and in the endometrium, which may be part of the etiology of the positive effects of n-3 FA on the reproductive system in dairy cows.http://www.sciencedirect.com/science/article/pii/S0022030225000037dairy cowsendocannabinoidsfollicleomega-3uterus |
| spellingShingle | P. dos S. Silva Y. Butenko G. Kra S. Malitsky M. Itkin Y. Levin U. Moallem M. Zachut Omega-3 fatty acid supplementation from late pregnancy to early lactation attenuates the endocannabinoid system and immune proteome in preovulatory follicles and endometrium of Holstein dairy cows Journal of Dairy Science dairy cows endocannabinoids follicle omega-3 uterus |
| title | Omega-3 fatty acid supplementation from late pregnancy to early lactation attenuates the endocannabinoid system and immune proteome in preovulatory follicles and endometrium of Holstein dairy cows |
| title_full | Omega-3 fatty acid supplementation from late pregnancy to early lactation attenuates the endocannabinoid system and immune proteome in preovulatory follicles and endometrium of Holstein dairy cows |
| title_fullStr | Omega-3 fatty acid supplementation from late pregnancy to early lactation attenuates the endocannabinoid system and immune proteome in preovulatory follicles and endometrium of Holstein dairy cows |
| title_full_unstemmed | Omega-3 fatty acid supplementation from late pregnancy to early lactation attenuates the endocannabinoid system and immune proteome in preovulatory follicles and endometrium of Holstein dairy cows |
| title_short | Omega-3 fatty acid supplementation from late pregnancy to early lactation attenuates the endocannabinoid system and immune proteome in preovulatory follicles and endometrium of Holstein dairy cows |
| title_sort | omega 3 fatty acid supplementation from late pregnancy to early lactation attenuates the endocannabinoid system and immune proteome in preovulatory follicles and endometrium of holstein dairy cows |
| topic | dairy cows endocannabinoids follicle omega-3 uterus |
| url | http://www.sciencedirect.com/science/article/pii/S0022030225000037 |
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