The role of omega-3 and omega-6 metabolites during pregnancy


During normal pregnancy, inflammation is associated with placentation, implantation and delivery. Uncontrolled inflammation can have serious adverse effects on mothers and infants. Therefore, understanding the molecular interactions that occur during controlled inflammation during pregnancy is essential.

Research: Something fishy: how lipid mediators affect the maternal-fetal interface and neonatal development. Image credit: ldutko / Shutterstock

Dietary omega-3 and omega-6 fatty acids are metabolized into bioactive compounds that affect inflammation.in a recent magazine biomedical study, Scientists reviewed the existing literature and compiled findings related to the role of omega-3 and omega-6 metabolites during pregnancy.

What is inflammation?

Inflammation is an important biological activity necessary to protect the body from infection. It has been demonstrated that inflammation suppresses and prevents infection. It is also involved in resolving tissue damage and promoting tissue repair and regeneration.

Inflammation is driven by chemokines and cytokines that affect blood vessels, tissues, and nerves. Signs of inflammation can be determined by the five most common signs: pain, fever, loss of function, redness, and swelling. Inflammatory responses are regulated by pro- and anti-inflammatory molecules. Concomitant synthesis of anti-inflammatory molecules has been observed to alleviate inflammation.

Diet can help reduce inflammation. Omega-3 fatty acids (n-3 fatty acids) and omega-6 fatty acids (n-6 fatty acids) are involved in several important bodily functions, including regulation of the inflammatory system.

Mo et al. Stage 1 of immunological events that occur during pregnancy. Implantation is dependent on the presence of proinflammatory cytokines, chemokines and other mediators that invade the uterine wall. During placentation, there is a dynamic relationship between the uterine wall and the placenta for trophoblast differentiation and proper placental development. Inflammation is indicated by red dots in the figure.  Diagram created with BioRender.Mo et al. Stage 1 of immunological events that occur during pregnancy. Implantation is dependent on the presence of proinflammatory cytokines, chemokines and other mediators that invade the uterine wall. During placentation, there is a dynamic relationship between the uterine wall and the placenta for trophoblast differentiation and proper placental development. Inflammation is indicated by red dots in the figure. Diagram created with BioRender.

Relationship between inflammation and nutrition during pregnancy

The body relies heavily on inflammation during three different stages of pregnancy. First, early pregnancy (1st and 2nd trimester) when implantation and placentation occur. At this stage, inflammation enables placental cells to establish maternal and fetal blood flow. Second, the second trimester, the period during which the fetus grows rapidly within an anti-inflammatory environment. Finally, the third trimester of pregnancy is inflamed as the mother begins to prepare for childbirth.

The roles of n-3 FAs and n-6 ​​FAs ​​in various stages of inflammation have been elucidated. Dietary intake of essential FAs such as linoleic acid (LA) and alpha-linolenic acid (ALA) is important. LA is the major source of dihomo-γ-linolenic acid (DGLA) and arachidonic acid (AA). Similarly, ALA is the parent nutrient from which eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are synthesized. In most cases, inefficient conversion of ALA to EPA or DHA has been observed. That is, 8-10% of ALA was found to be converted to EPA and less than 1% to DHA. Therefore, it is important to get DHA and EPA from your diet to reach recommended levels.

There are no consistent guidelines regarding the optimal daily intake of n-3 fatty acids during pregnancy. However, EPA and DHA are recommended around 200g per day for him. In the United States, pregnant women’s diets are often high in n-6 FAs ​​and low in n-3 FAs, increasing the risk of poor maternal and fetal outcomes due to inflammatory dysregulation.

Mo et al. Stages 2-3 of immunological events that occur during pregnancy. Stage 2 is defined by a balance of pro- and anti-inflammatory mediators and involves a transition to an anti-inflammatory environment. Inflammation is necessary to prevent fetal infection and rejection. Stage 3 is the pro-inflammatory condition that prepares for labor and delivery. Cytokines and mediators remodel the cervix, infiltrate the uterus and participate in uterine contractions. Blue dots represent anti-inflammatory molecules and red dots represent pro-inflammatory molecules. The figure was created with Violender.Mo et al. Stages 2-3 of immunological events that occur during pregnancy. Stage 2 is defined by a balance of pro- and anti-inflammatory mediators and involves a transition to an anti-inflammatory environment. Inflammation is necessary to prevent fetal infection and rejection. Stage 3 is the pro-inflammatory condition that prepares for labor and delivery. Cytokines and mediators remodel the cervix, infiltrate the uterus and participate in uterine contractions. Blue dots represent anti-inflammatory molecules and red dots represent pro-inflammatory molecules. The figure was created with Violender.

Role of Omega-3 and Omega-6 Fatty Acids During Pregnancy

A large body of evidence demonstrates the importance of n-3 FAs during pregnancy. For example, n-3 FA DHA is important for proper development of the fetal nervous system and retina. AA, a type of n-6 FA, accumulates in the fetal brain and is essential for its development. Nonetheless, imbalances in n-3 and n-6 ​​FA intakes can affect the homeostatic balance within the maternal and infant bodies.

As mentioned above, n-6 FA and n-3 FA are involved in the inflammatory cascade. Parental n-6 and n-3 FAs compete with cyclooxygenase (COX), lipoxygenase (LOX), or cytochrome P450 enzymes (CYP450) to generate eicosanoids. n-6 FAs ​​normally synthesize pro-inflammatory eicosanoids, whereas n-3 FA metabolites are anti-inflammatory.

The main function of eicosanoids is to increase the pro-inflammatory environment or induce tissue repair and degradation processes. Additionally, these metabolites regulate inflammation during pregnancy. However, further research is needed to understand the function of eicosanoids in the normal, non-pregnant state.

AA produces various intermediates through various enzymatic reactions. For example, the COX pathway synthesizes two series of prostanoids (eg, prostaglandins) that influence platelet aggregation, T-cell differentiation, and inflammatory cytokines. In addition, the LOX pathway is a bioactive leukotriene and monohydroxyeicosatetraenoic acid from hydroperoxyeicosatetraenoic acid (HpETE) that induces the generation of chemokinesis and chemotactic responses in eosinophils and neutrophils. It is related to the generation of -12 (HETE).

How are pregnancy outcomes related to inflammation?

Several mechanisms are associated with premature birth. Chemokines and cytokines are among the most important factors involving premature birth due to inflammation/infection. In addition, they also increase placental membrane permeability during bacterial infections (eg, chorioamnionitis), increasing the risk of premature membrane rupture and synovitis. AA-derived oxylipins are also associated with prematurity.

Infants exposed to intrauterine inflammation had a higher risk of developing intraventricular hemorrhage, chronic lung disease, periventricular leukomalacia, and necrotizing enterocolitis compared with preterm infants not exposed to inflammation.

Preeclampsia (PE) is a clinical condition characterized by proteinuria, inflammation, placental defect, and endothelial dysfunction in the second trimester of pregnancy. N-6 FA metabolites have been found primarily in plasma and placental samples from preeclamptic women.



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