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

Authors: CHASSEN, STEPHANIE - University Of Colorado; SNODGRASS, ISABEL - University Of California, Davis; DILLON, MAIREAD - University Of Colorado; DAOUD, NANCY - University Of California, Davis; MORISSEAU, CHRISTOPHE - University Of California, Davis; RAYMOND-WHISH, STEPHANIE - University Of Colorado; HAMMOCK, BRUCE - University Of California, Davis; Newman, John; POWELL, THERESA - University Of Colorado

Submitted to: Prostaglandins Leukotrienes and Essential Fatty Acids
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/10/2026
Publication Date: 7/11/2026
Citation: Chassen, S.S., Snodgrass, I.F., Dillon, M., Daoud, N., Morisseau, C., Raymond-Whish, S., Hammock, B.D., Newman, J.W., Powell, T.L. 2026. Placental abundance of arachidonic acid metabolites is reduced in preterm placentas but is not altered in fetal growth restriction. Prostaglandins Leukotrienes and Essential Fatty Acids. 210. Article 102761. https://doi.org/10.1016/j.plefa.2026.102761.
DOI: https://doi.org/10.1016/j.plefa.2026.102761

Interpretive Summary: Arachidonic acid is a long chain polyunsaturated fatty acid and precursor to bioactive lipid molecules that influence inflammation and vasoregulation. In the placenta, arachidonic acid metabolites (including oxylipins) play a role in maternal adaptation to pregnancy and fetoplacental development. Many of these compounds found in blood plasma are considered biomarkers of both pregnancy complications and timing of delivery. While several enzymes involved in arachidonic acid metabolism have been studied in the human placenta, the role of one, the soluble epoxide hydrolase (sEH) responsible for degradation of anti-inflammatory metabolites is less well studied. Placenta tissue samples were collected in from women with healthy term pregnancy (HT0 and from pregnancies complicated by preterm birth (PT) or low birth weight (i.e., fetal growth restriction (FGR), birth weight <5th centile). Prostaglandins and other proinflammatory arachidonic acid metabolites were lower in placentas from PT as compared to HT (p<0.05). There were no differences between HT and FGR groups for any of the measured lipids. The increase in placental content of oxylipins across the second half of pregnancy likely supports late phase infant growth and labor. Studies of lipid signaling must include carefully gestational age-matched controls to identify changes of pathologic interest.

Technical Abstract: Arachidonic acid is a long chain polyunsaturated fatty acid and precursor to bioactive lipid molecules that influence inflammation and vasoregulation. In the placenta, arachidonic acid metabolites (including oxylipins) play a role in maternal adaptation to pregnancy and fetoplacental development and are considered biomarkers of both pregnancy complications and timing of delivery. Several enzymes involved in the arachidonic acid synthesis and degradation pathway (including COX, LOX, CYP) have been studied in the human placenta, but the role of epoxide hydrolase enzymes (responsible for degradation of CYP-dependent metabolites called epoxyeicosatrienoic acids) is less well studied. We hypothesized that fetal growth and gestational age affect placental metabolism of arachidonic acid and placental expression and activity of epoxide hydrolases. Placenta tissue samples were collected in two cohorts from women with healthy term pregnancy (HT0 and from pregnancies complicated by preterm birth (PT) or fetal growth restriction (FGR, birth weight <5th centile). Lipids (arachidonic acid-derived oxylipins) were extracted from placental homogenate and quantified using LC-MS/MS. Placental abundance of arachidonic acid metabolites in the COX, LOX, sEH and autooxidation pathways were lower in PT as compared to HT (p<0.05), while no differences were found in CYP pathway lipids. There were no significant differences between HT and FGR groups for any of the measured lipids. The increase in placental content of oxylipins across the second half of pregnancy likely serves several roles including labor initiation signaling, xenobiotic protection and increased transfer of important lipids during late pregnancy to support brain and somatic growth, indicating studies of lipid signaling must include carefully gestational age-matched controls in order to identify changes of pathologic interest.