Omega-6 and Omega-3 Fatty Acid-Derived Oxylipins from the Lipoxygenase Pathway in Maternal and Umbilical Cord Plasma at Delivery and Their Relationship with Infant Growth

Abstract

Omega-3 and omega-6 fatty acids are important for neonatal development and health. One mechanism by which omega-3 and omega-6 fatty acids exert their effects is through their metabolism into oxylipins and specialized pro-resolving mediators. However, the influence of oxylipins on fetal growth is not well understood. Therefore, the objective of this study was to identify oxylipins present in maternal and umbilical cord plasma and investigate their relationship with infant growth. Liquid chromatography–tandem mass spectrometry was used to quantify oxylipin levels in plasma collected at the time of delivery. Spearman’s correlations highlighted significant correlations between metabolite levels and infant growth. They were then adjusted for maternal obesity (normal body mass index (BMI: ≤30 kg/m2) vs. obese BMI (>30 kg/m2) and smoking status (never vs. current/former smoker) using linear regression modeling. A p-value < 0.05 was considered statistically significant. Our study demonstrated a diverse panel of oxylipins from the lipoxygenase pathway present at the time of delivery. In addition, both omega-3 and omega-6 oxylipins demonstrated potential influences on the birth length and weight percentiles. The oxylipins present during pregnancy may influence fetal growth and development, suggesting potential metabolites to be used as biomarkers for infant outcomes.

Something Smells Fishy: How Lipid Mediators Impact the Maternal–Fetal Interface and Neonatal Development

“…However, progesterone cannot block infection-induced inflammation, and concerns remain regarding route administration, bioavailability, and its association with increased incidence of stillbirths [94]. Other drugs such as cytokine-suppressive anti-inflammatory drugs (CSAIDS), anti-inflammatory prostaglandin 15-deoxy-D (12,14), prostaglandin J2 (15dPGJ2), and antibody-based TNF-α biologics are being studied for their ability to modulate inflammatory pathways and influence prematurity [18]. A large gap remains in the effective prevention and treatment of preterm labor.…”

“…A brief schema of n-3 and n-6 lipid metabolism, highlighting key downstream FAs and their subsequent bioactive metabolites (i.e., EPA, DHA). Figure copied from Thompson et al [14]. ALA, alpha-linolenic acid; EPA, eicosapentaenoic acid; DPA, docosapentaenoic acid; DHA, docosahexaenoic acid; HEPE, hydroxyeicosapentaenoic acid; DiHEPE, dihydroxy-eicosapentaenoic acid; HDHA, hydroxydocosahexaenoic acid; LA, linoleic acid; DGLA, dihomo-γ-linolenic acid; AA, arachidonic acid; LX, lipoxin; HODE, hydroxy-octadecadienoic acid; KODE, keto-octadecadienoic acid; HETrE, hydroxy-eicosatrienoic acids; LT, leukotriene.…”

Oxylipins as Potential Regulators of Inflammatory Conditions of Human Lactation

“…However, only a single report has been found reporting circulating oxylipin profiles in lactating humans [ 65 ] ( Table 3 ), and that study reported vitamin A status, not lactation or breastfeeding measures, as outcomes. A few studies have reported circulating oxylipins during pregnancy in humans [ 66 , 67 , 68 , 69 , 70 ], showing potential associations with infant growth [ 70 ] and pre-term birth [ 67 , 69 ], but have not investigated breastfeeding outcomes. More work is needed to characterize the systemic oxylipin profile in human circulation during lactation.…”

Identification of omega-3 oxylipins in human milk-derived extracellular vesicles with pro-resolutive actions in gastrointestinal inflammation

“…Both ω-3 and ω-6 oxylipins are involved in the initiation and resolution of inflammatory processes [10]. In addition, some oxylipins are precursors of specialized pro-resolving and cytoprotective mediators (SPMs), in particular, ω3-derived oxylipins (resolvins, maresins, and protectins) with anti-inflammatory effects, which are involved in the resolution process following tissue injury [11], [12], [13].…”