Omega-3 Fatty Acid Supplementation, Pro-Resolving Mediators, and Clinical Outcomes in Maternal-Infant Pairs

Nordgren, Tara M.; Berry, Ann Anderson; Ormer, Matthew Van; Zoucha, Samuel; Elliott, Elizabeth J; Johnson, Rebecca L.; McGinn, Elizabeth; Cave, Caleb; Rilett, Katherine; Weishaar, Kara; Maddipati, Sai Sujana; Appeah, Harriet; Hanson, Corrine

doi:10.3390/nu11010098

Cited by 18 publications

(18 citation statements)

References 28 publications

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“…The identification that omega-3 fatty acids are metabolized into bioactive pro-inflammation resolution lipids, SPM [7], provides a potential link between the known benefits of omega-3 fatty acid supplementation in pregnancy and their conferred protection from negative inflammation-associated perinatal outcomes. Of note, we recently identified that maternal circulating blood collected at delivery has significantly higher levels of SPM RvD1 and RvD2 compared to cord blood, suggesting that the placenta could be a site of action for maternal SPM [16]. Through the investigations described herein, we have identified the placenta as a site of action for SPM, with key actions on specific placental cell types including placental vascular smooth muscle and EVT that could confer protection against inflammatory injury and disease.…”

Section: Discussionmentioning

confidence: 77%

“…Also, a recent study identified that supplementation of omega-3 fatty acids during pregnancy increases precursors of SPM in newborns [19]. Adding to these studies are our recent findings that RvD1 and RvD2 levels were significantly elevated in maternal blood collected at labor as compared to cord blood, suggesting the placenta as a potential site of action for maternal circulating SPM [16].…”

Section: Discussionmentioning

confidence: 99%

“…These breastmilk-derived SPM were also found to be highly bioactive with potent anti-inflammatory and pro-resolving actions when used as treatments in vitro and in vivo [12]. Furthermore, we recently found increased levels of SPM in maternal and cord blood at the time of delivery, with high RvD1 and RvD2 levels associated with adverse clinical outcomes [16]. Of interest, RvD1 and RvD2 levels were significantly elevated in maternal blood as compared to cord blood, suggesting the placenta as a potential site of action for maternal circulating SPM [16].…”

Section: Introductionmentioning

confidence: 99%

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Omega-3 Fatty Acid-Derived Resolvin D2 Regulates Human Placental Vascular Smooth Muscle and Extravillous Trophoblast Activities

Ulu

Sahoo

Yuil‐Valdes

et al. 2019

IJMS

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Omega-3 fatty acids are important to pregnancy and neonatal development and health. One mechanism by which omega-3 fatty acids exert their protective effects is through serving as substrates for the generation of specialized pro-resolving lipid mediators (SPM) that potently limit and resolve inflammatory processes. We recently identified that SPM levels are increased in maternal blood at delivery as compared to umbilical cord blood, suggesting the placenta as a potential site of action for maternal SPM. To explore this hypothesis, we obtained human placental samples and stained for the SPM resolvin D2 (RvD2) receptor GPR18 via immunohistochemistry. In so doing, we identified GPR18 expression in placental vascular smooth muscle and extravillous trophoblasts of the placental tissues. Using in vitro culturing, we confirmed expression of GPR18 in these cell types and further identified that stimulation with RvD2 led to significantly altered responsiveness (cytoskeletal changes and pro-inflammatory cytokine production) to lipopolysaccharide inflammatory stimulation in human umbilical artery smooth muscle cells and placental trophoblasts. Taken together, these findings establish a role for SPM actions in human placental tissue.

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Section: Discussionmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Omega-3 Fatty Acid-Derived Resolvin D2 Regulates Human Placental Vascular Smooth Muscle and Extravillous Trophoblast Activities

Ulu

Sahoo

Yuil‐Valdes

et al. 2019

IJMS

Self Cite

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“…Many immune cell types produce SPMs [ 56 , 57 , 58 , 59 ]. SPMs have been measured in human plasma including from pregnant women [ 60 ], umbilical cord [ 60 , 61 , 62 ], infants [ 61 ] and children [ 61 , 62 ]. Human breast milk has been reported to contain SPMs [ 63 , 64 , 65 ].…”

Section: Long-chain Polyunsaturated Fatty Acids Lipid Mediators mentioning

confidence: 99%

Long-Chain Polyunsaturated Fatty Acids (LCPUFAs) and the Developing Immune System: A Narrative Review

2021

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The immune system is complex: it involves many cell types and numerous chemical mediators. An immature immune response increases susceptibility to infection, whilst imbalances amongst immune components leading to loss of tolerance can result in immune-mediated diseases including food allergies. Babies are born with an immature immune response. The immune system develops in early life and breast feeding promotes immune maturation and protects against infections and may protect against allergies. The long-chain polyunsaturated fatty acids (LCPUFAs) arachidonic acid (AA) and docosahexaenoic acid (DHA) are considered to be important components of breast milk. AA, eicosapentaenoic acid (EPA) and DHA are also present in the membranes of cells of the immune system and act through multiple interacting mechanisms to influence immune function. The effects of AA and of mediators derived from AA are often different from the effects of the n-3 LCPUFAs (i.e., EPA and DHA) and of mediators derived from them. Studies of supplemental n-3 LCPUFAs in pregnant women show some effects on cord blood immune cells and their responses. These studies also demonstrate reduced sensitisation of infants to egg, reduced risk and severity of atopic dermatitis in the first year of life, and reduced persistent wheeze and asthma at ages 3 to 5 years, especially in children of mothers with low habitual intake of n-3 LCPUFAs. Immune markers in preterm and term infants fed formula with AA and DHA were similar to those in infants fed human milk, whereas those in infants fed formula without LCPUFAs were not. Infants who received formula plus LCPUFAs (both AA and DHA) showed a reduced risk of allergic disease and respiratory illness than infants who received standard formula. Studies in which infants received n-3 LCPUFAs report immune differences from controls that suggest better immune maturation and they show lower risk of allergic disease and respiratory illness over the first years of life. Taken together, these findings suggest that LCPUFAs play a role in immune development that is of clinical significance, particularly with regard to allergic sensitisation and allergic manifestations including wheeze and asthma.

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“…Both aspirintriggered and non-aspirin-triggered SPM have biological activity (88)(89)(90) . A variety of SPM have been reported in human blood (91)(92)(93) , including umbilical cord blood (94,95) , adipose tissue (96) , breast milk (97) and synovial fluid (98) . Supplemental EPA and DHA has been shown to result in higher concentrations of some SPM in human blood (91)(92)(93)99) .…”

Section: N-3 Pufa Lipid Rafts Nfκb Activation and Inflammatory Cytomentioning

confidence: 99%

n-3 PUFA and inflammation: from membrane to nucleus and from bench to bedside

Calder

2020

Proc. Nutr. Soc.

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Inflammation is a normal part of the immune response and should be self-limiting. Excessive or unresolved inflammation is linked to tissue damage, pathology and ill health. Prostaglandins and leukotrienes produced from the n-6 fatty acid arachidonic acid are involved in inflammation. Fatty acids may also influence inflammatory processes through mechanisms not necessarily involving lipid mediators. The n-3 fatty acids EPA and DHA possess a range of anti-inflammatory actions. Increased content of EPA and DHA in the membranes of cells involved in inflammation has effects on the physical nature of the membranes and on the formation of signalling platforms called lipid rafts. EPA and DHA interfere with arachidonic acid metabolism which yields prostaglandins and leukotrienes involved in inflammation. EPA gives rise to weak (e.g. less inflammatory) analogues and both EPA and DHA are substrates for the synthesis of specialised pro-resolving mediators. Through their effects on early signalling events in membranes and on the profile of lipid mediators produced, EPA and DHA alter both intracellular and intercellular signals. Within cells, this leads to altered patterns of gene expression and of protein production. The net result is decreased production of inflammatory cytokines, chemokines, adhesion molecules, proteases and enzymes. The anti-inflammatory and inflammation-resolving effects of EPA and DHA are relevant to both prevention and treatment of human diseases that have an inflammatory component. This has been widely studied in rheumatoid arthritis where there is good evidence that high doses of EPA + DHA reduce pain and other symptoms.

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Omega-3 Fatty Acid Supplementation, Pro-Resolving Mediators, and Clinical Outcomes in Maternal-Infant Pairs

Cited by 18 publications

References 28 publications

Omega-3 Fatty Acid-Derived Resolvin D2 Regulates Human Placental Vascular Smooth Muscle and Extravillous Trophoblast Activities

Omega-3 Fatty Acid-Derived Resolvin D2 Regulates Human Placental Vascular Smooth Muscle and Extravillous Trophoblast Activities

Long-Chain Polyunsaturated Fatty Acids (LCPUFAs) and the Developing Immune System: A Narrative Review

n-3 PUFA and inflammation: from membrane to nucleus and from bench to bedside

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