Placental abundance of arachidonic acid metabolites is reduced in preterm placentas but is not altered in fetal growth restriction

Arachidonic acid is a long chain polyunsaturated fatty acid and precursor to bioactive lipid molecules contributing to inflammation and vasoregulation. Placental arachidonic acid metabolites (including oxylipins) are involved in maternal adaptation to pregnancy and fetoplacental development, and are considered biomarkers of pregnancy complications and delivery timing. Arachidonic acid metabolic pathway enzymes (including COX, LOX, CYP) have been studied in human placenta, but the role of epoxide hydrolases (responsible for degradation of CYP-dependent metabolites—epoxyeicosatrienoic acids) is not as widely researched. We hypothesized that fetal growth restriction (FGR) and gestational age both independently affect placental arachidonic acid metabolism and expression and activity of epoxide hydrolases. Placenta tissue samples were collected: Cohort 1 included women with healthy term pregnancy (HT), preterm birth (PT), or FGR (birth weight <5 th centile). Cohort 2 included women with HT pregnancy or FGR (same criteria). Cohorts were analyzed separately. Placental lipids (arachidonic acid-derived oxylipins) were extracted and quantified using LC-MS/MS. Placental abundance of arachidonic acid metabolites in COX, LOX, sEH and autooxidation pathways were lower in PT compared to HT (p<0.05). No differences were found in CYP pathway lipids and no significant differences detected between HT and FGR for any measured lipid. Increased placental content of oxylipins across the second half of pregnancy likely contributes to labor initiation signaling, xenobiotic protection and, importantly, increased lipid transfer to support fetal brain and somatic growth. Our data indicates that studies of placental lipid signaling must include carefully gestational age-matched controls in order to correctly identify changes of pathologic interest.